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CAS No. : | 1027-35-6 | MDL No. : | MFCD09998956 |
Formula : | C14H17NO3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | XLKXIFXOWMGWNT-UHFFFAOYSA-N |
M.W : | 247.29 | Pubchem ID : | 274831 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium tert-butylate; In toluene; for 2h;Cooling with ice; | The crude 1127.324 g compound (c) is dissolved in 2.5 L toluene without water, 243.028g tert potassium butanolate is added gradually under ice bath, stirred for 2h, TLC was carried out to detect the completion of the reaction, 4M HCl in ice bath was added, PH in acidic was adjusted to PH=8 using saturated sodium bicarbonate, extracted with ethyl acetate, dried using anhydrous Na2SO4, filtered, and spin-dried to obtain 376.7g pink solid compound (d), yield 98percent. |
78% | With potassium tert-butylate; In toluene; at 0℃; for 2h; | Above-prepared ethyl 3-[N-benzyl-N-(ethoxycarbonylmethyl)amino]propionate (14.0 g, 0.0479 mol) was dissolved in toluene (100 mL), and the solution was mixed with potassium tert-butoxide (5.9 g, 0.0525 mol) gradually added under ice-cooling, followed by stirring under ice-cooling for two hours. The reaction mixture was mixed with diluted hydrochloric acid (about 1 mol/L, 100 mL) under ice-cooling, followed by shaking and separation, to yield an aqueous layer. Saturated aqueous sodium bicarbonate solution (300 mL) was added dropwise to the aqueous layer, and ethyl acetate (400 mL) was further added thereto, followed by shaking and separation. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, to thereby yield ethyl 1-benzyl-4-oxopyrrolidine-3-carboxylate (9.23 g, in a yield of 78percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
By following the same procedure but using the corresponding ethyl N,N-disubstituted-glycinates the following 1-substituted 4-ethoxycarbonylpyrrolidine-3-ones are synthesised....4-ethoxycarbonyl-1-(3,4,5-trichlorophenyl)pyrrolidine-3-one,4-ethoxycarbonyl-1-(2,4,6-tribromophenyl)pyrrolidine-3-one,4-ethoxycarbonyl-1-(2,4,5-tribromophenyl)pyrrolidine-3-one,4-ethoxycarbonyl-1-(3,4,5-tribromophenyl)pyrrolidine-3-one,4-ethoxycarbonyl-1-benzylpyrrolidine-3-one,4-ethoxycarbonyl-1-(2-methoxybenzyl)pyrrolidine-3-one,4-ethoxycarbonyl-1-(3-methoxybenzyl)pyrrolidine-3-one,4-ethoxycarbonyl-1-(4-methoxybenzyl)pyrrolidine-3-one,... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; In methanol; ethyl acetate; | Preparation of 1-Benzyl-4-hydroxymethyl-pyrrolidin-3-ol (I-4c): Intermediate I-4b (0.0162 mol, 4.0 g, 1eq) was dissolved in 60 mL of MeOH and the cooled to 0° C. NaBH4 (0.0971, 3.67 g, 6 eq) was added in 250 mg portions over an hour period. The mixture was warmed to room temperature and allowed to stir overnight. The MeOH was removed in vacuo and the residue was taken up in EtOAc (60 mL) and 2N NaOH (20 mL). The mixture was shaken for approximately 2 to 3 minutes in a separation funnel. The organic phase was separated and the aqueous phase was washed with 2*50 mL more EtOAc. The organic layers were combined, dried over sodium sulfate and concentrated in vacuo to a pale yellow oil which was placed under high vacuum for 2 hours to afford a clear pale yellow gum 2.06 g (65percent). | |
1.88 g | With methanol; sodium tetrahydroborate; at 0 - 20℃; | To a stirred solution of <strong>[1027-35-6]ethyl 1-benzyl-4-oxopyrrolidine-3-carboxylate</strong> (5 g, 20.2 mmol)in MeOH (75 mL) at 0 °C, NaBH4 (4.58 g, 121.2 mmol) was added in portion of 250 mg over30?. Then the solution was warmed to RT and stirred ON. Solvent was removed under vacuum. The residue was dissolved in EtOAc (75 mL) and NaOH 2 M (25 mL), organic phase was separated and the aqueous phase was washed again with EtOAc (60 mL x2). Combined organics were dried over Na2504 and concentrated to obtain 5.7 g of a yellow oil that was purified by FCon 5i02 cartridge (eluting from DCM to MeOH 100percent) to obtain 1.88 g of title compound as yellow oil (p133). MS (m/z):208.2 [IVll{]t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With hydrogenchloride; sodium cyanoborohydride; In tetrahydrofuran; methanol; benzene; | (1) Preparation of 1-benzyl-3-carboethoxy-4-benzylaminopyrrolidine 24.7 g of 1-benzyl-3-carboethoxy-4-pyrrolidone and 10.7 g of benzylamine were added to 100 ml of benzene, and then dehydrated with Dean-Stark distillation apparatus. The residual benzene was evaporated. The residue was dissolved in 200 ml of tetrahydrofuran, and then a small amount of methyl orange was added. To this was added methanol saturated with hydrogen chloride to adjust the pH to about 4, and then 7 g of sodium cyanoborohydride was added thereto. A solution of methanol saturated with hydrogen chloride was added dropwise to the reaction solution with stirring until the pink-color of the solution did not disappear. The reaction solution was basified with 15percent aqueous caustic soda solution, and then the reaction mixture was diluted with ether, after which the aqueous layer was separated the aqueous layer was removed by addition of ether. The organic layer was dried over anhydrous magnesium sulfate, evaporated under reduced pressure, and then subjected to silica gel column chromatography (hexane:ethyl acetate, 5:1 (v/v)) to obtain 24 g of the desired compound (yield: 71percent). 1 H-NMR (CDCl3, delta): 1.27(3H, t), 2.6~3.0(5H, m), 3.57(1H, m), 3.63(2H, d), 3.80(2H, s), 4.18(2H, q), 7.31(10H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | A. 2-Benzyl-4-oxo-9-hydroxy-7-(3-methyl-2-octyl)-1,2,3,4tetrahydro[ 1]benzopyrano[ 3,4-c]pyrrole This first intermediate was prepared by the following reaction: SPC5 The ethyl 1-benzyl-4-pyrrolidone-3-carboxylate was prepared in 40percent yield (5 g) from 14.7 g of diethyl 13. benzyl.3.azaadipate and 5.6 g of potassium t-butoxide according to the procedure of E. Jaeger and J. H. Beal, J. Org. Chem. 30, 742 (1965). It was a colorless, slightly cloudy oil with nD25 1.5147 (lit. nD25 1.5264). The infrared spectrum was the same as the published value. The 5-(3-methyl-2-octyl) resorcinol was prepared by the method of Adams, MacKenzie and Loewe, JACS 70, 664-8 (1948). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With hydrogenchloride; In tetrahydrofuran; methanol; benzene; | (1) Preparation of 1-benzyl-3-carboethoxy-4-benzylaminopyrrolidine 24.7g of 1-benzyl-3-carboethoxy-4-pyrrolidone and 10.7g of benzylamine were added to 100ml of benzene, and then dehydrated with Dean-Stark distillation apparatus. The residual benzene was evaporated The residue and a small amount of methyl orange were dissolved in 200ml of tetrahydrofuran, and methanol saturated with hydrogen chloride was adjusted to about pH 4, and then 7g of sodium borocyanohydride was added thereto. A solution of methanol saturated with hydrogen chloride was added dropwise to the reaction solution with stirring until the pink-color of the solution did not disappear. The reaction solution was basified with 15percent aqueous caustic soda solution, and then the aqueous layer was removed by addition of ether. The organic phase was dried over anhydrous magnesium sulfate, evaporated under reduced pressure, and then subjected to silica gel column chromatography (hexane:ethyl acetate, 5: 1(v/v)) to obtain 24g of the desired compound (yield:71 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With potassium tert-butylate; In tert-butyl alcohol; at 100℃; for 6h; | 6-Benzyl-2-isopropyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-ol. To a solution of 1-benzyl-4-oxo-pyrrolidine-3-carboxylic acid ethyl ester hydrochloride (U.S. Pat. No. 3,312,716; 0.568 g, 2.30 mmol) in tert-BuOH was added isobutyramidine hydrochloride (0.282 g, 2.30 mmol) and KOtBu (0.516 g, 4.6 mmol). After heating for 6 h at 100° C., the reaction was cooled to rt, concentrated, diluted with water and washed with Et2O. The organic layer discarded. The aqueous layer was adjusted to pH 7 and extracted with Et2O. The organic layers were then dried and concentrated to give 0.145 g (23percent) of the title compound of yellow solid that was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With sodium methylate; In methanol; ethanol; for 24h;Heating / reflux; | Ethyl 1-benzyl-4-oxopyrrolidine-3-carboxylate (9.23 g, 0.0372 mol) prepared according to Reference Example 2 was dissolved in ethanol (170 mL), and the solution was mixed with urea (11.2 g, 0.186 mol) and a solution of sodium methoxide in methanol (about 28percent, 25 g), followed by stirring under reflux for twenty-four hours. The reaction mixture was mixed with water (100 mL), followed by stirring at room temperature. Diluted hydrochloric acid (about 1 mol/L, 100 mL) was added dropwise to the reaction mixture. The precipitated crystals were collected by filtration, and the collected crystals were washed with water (100 mL). The crystals were dried under reduced pressure and thereby yielded 6-benzyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine-2,4(1H,3H)-dione (3.93 g, in a yield of 43percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With triethylamine; In tetrahydrofuran; | Embodiment 6 Preparation of 1-ethoxycarbonyl-4-(3-chloropropyl)-3-pyrrolidone <strong>[1027-35-6]1-benzyl-4-ethoxycarbonyl-3-pyrrolidone</strong> (2.5 g, 10.1 mmol) is dissolved in 25 ml tetrahydrofuran and then cooled by ice water bath, triethylamine (2 g, 20.2 mmol) is added and stirring is performed for 30 minutes, 1-chloro-3-iodopropane (4.12 g, 20.2 mmol) is dripped, this dripping is finished 30 minutes later, afterwards, the temperature is raised to room temperature for the purpose of continuous reaction for 18 hours. Extraction is carried out by methylene dichloride (10 ml*3 times) at the end of reaction, organic phase is combined and dried by anhydrous sodium sulfate, and the solvent is dried by concentration under reduced pressure to obtain oily product, which is then purified by column chromatography to obtain oily product (6-1) (2.12 g, 6.57 mmol, yield 65percent). 1H NMR (500 MHz, CDCl3) delta7.34-7.27 (m, 5H), 4.17 (q, J=7.1 Hz, 2H), 3.71 (s, 2H), 3.48-3.51 (m, 2H), 3.40 (d, J=9.6 Hz, 1H), 3.19 (d, J=17.2 Hz, 1H), 2.99 (d, J=17.2 Hz, 1H), 2.73 (d, J=9.6 Hz, 1H), 2.04-2.02 (m, 1H), 1.92-1.89 (m, 2H), 1.71-1.69 (m, 1H), 1.24 (t, J=7.1 Hz, 3H). MS-ESI: m/z: 324 (M++1). |
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