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CAS No. : | 85909-08-6 | MDL No. : | MFCD00674099 |
Formula : | C9H15NO3 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | GJJYYMXBCYYXPQ-UHFFFAOYSA-N |
M.W : | 185.22 | Pubchem ID : | 379000 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
Under an argon atmosphere, <strong>[1259396-11-6]5-bromo-2-methylthiophene-3-carboxylic acid methyl ester</strong> (2.00 g) was dissolved in tetrahydrofuran (9.47 mL), isopropylmagnesium bromide (12.9 mL) was added dropwise thereto at -40 C., and stirring was conducted for 1.5 hours. A solution of 2-oxopyrrolidine-1-carboxylic acid t-butyl ester (1.89 g) in tetrahydrofuran (11.2 mL) was added dropwise at -40 C., and stirred at room temperature for 24 hours. The reaction liquid was cooled to -10 C., methanol (17.2 mL) was added thereto, sodium borohydrate (486 mg) was then added thereto in portions, and stirring was conducted for 15 minutes. A saturated aqueous ammonium chloride solution was added to the reaction liquid, and the reaction liquid was extracted with chloroform and dried over anhydrous sodium sulfate. Filtration was conducted, the filtrate was then concentrated under a reduced pressure, and the obtained residue was purified by silica gel chromatography (hexane/ethyl acetate=1/1) to give the title compound (2.13 g) as a yellow oily substance.1H-NMR (CDCl3) delta (ppm): 1.44 (9H, s), 1.51-1.69 (4H, m), 1.79-1.84 (1H, m), 2.70 (3H, s), 3.15-3.19 (1H, m), 3.83 (3H, s), 4.57-4.87 (1H, m), 7.26 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29.15% | With lithium hexamethyldisilazane; In tetrahydrofuran; at -70℃; for 0.5h;Inert atmosphere; | To THF (300 mL) is added LiHMDS (1.0 M, 6.80 L) at -70 under N2. Ethyl carbonochloridate (597.62 g, 5.51 mol) and tert-butyl 2-oxopyrrolidine-1-carboxylate (600.00 g, 3.24 mol) are added to the mixture at the same temperature and the mixture is stirred at -70 for 30 minutes. The reaction mixture is poured into an ice cold saturated solution of NH4Cl (1500 mL) and is separated. The aqueous layer is extracted with EtOAc (2×300 mL) and the combined organic extracts are washed with water (2×400 mL) , brine (2×400 mL) , dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is slurried with MTBE (500 mL) at 15 for 20 minutes and filtered. The filter cake is washed with MTBE (2×100 mL) and dried in vacuum to give the title compound (270.00 g, 944.50 mmol, 29.15) as a white solid.1H NMR (CDCl3) delta 1.32 (t, 3H) , 1.54 (s, 9H) , 2.25 (m, 1H) , 2.39 (m, 1H) , 3.54 (m, 1H) , 3.72 (m, 1H) , 3.90 (m, 1H) , 4.25 (q, 2H) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | To a solution of 11 (40.1g, 170mmol) in THF (150mL), a solution of i-PrMgBr (0.78M in THF, 229mL, 179mmol) was added dropwise at-40C and stirred at the same temperature for 1.5h. Next, a solution of 1-tert-butoxylcarbonyl-2-pyrrolidinone (31.6g, 170mmol) in THF (180mL) was added dropwise at-40C. After stirring at the same temperature for 1.5h and then stirring at room temperature for 1h, the reaction was quenched with saturated aqueous NH4Cl. The reaction mixture was extracted with AcOEt, and organic layer was washed with water and brine and dried over Na2SO4. After filtration, the solvent was concentrated under reduced pressure and the residue was recrystallized with AcOEt/n-hexane to give 29.5g (51%) of 22a as a pale-yellow solid: 1H NMR (400MHz, CDCl3) delta 7.98 (s, 1H), 4.64 (br s, 1H), 3.87 (s, 3H), 3.21 (q, J=6.3Hz, 2H), 2.92 (t, J=7.2Hz, 2H), 2.78 (s, 3H), 1.92 (quint, J=7.0Hz, 2H), 1.43 (s, 9H); MS (ESI) m/z: 340 (M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | A solution of isopropylmagnesium chloride in tetrahydrofuran (2 M, 29.7 mL, 59.4 mmol) was added in a drop-wise manner to a 5 C. solution of C1 (12 g, 54.0 mmol) in tetrahydrofuran (60 mL), at a rate that maintained the internal temperature of the reaction mixture below 10 C. The reaction was allowed to proceed at 5 C., and aliquots were quenched into methanol and analyzed by HPLC to monitor the extent of Grignard formation; once full conversion was observed (?5 to 10 minutes), a solution of tert-butyl 2-oxopyrrolidine-1-carboxylate (11.0 g, 59.4 mmol) in tetrahydrofuran (60 mL) was added drop-wise, again at a rate which maintained the reaction temperature below 10 C. The reaction was monitored by HPLC, and when no additional conversion was observed (?1 hour), it was quenched via careful addition of aqueous acetic acid (10%, 60 mL) and ethyl acetate (100 mL). The organic layer was separated and washed with saturated aqueous sodium chloride solution (2*100 mL), dried over magnesium sulfate, filtered, and concentrated to a mass of 35 g. Heptane (40 mL) was added, to a total volume of approximately 80 mL, and approximately 20 mL of solvent was removed via heating at atmospheric pressure. The mixture was slowly cooled to 20 C., and the resulting thick slurry was allowed to stir overnight at 20 C., whereupon it was filtered. The filter cake was rinsed with cold heptane (0 C., 30 mL) to afford the product as a white solid. Yield: 9.59 g, 34.1 mmol, 63%. 1H NMR (400 MHz, CDCl3) delta 7.79 (s, 1H), 4.72-4.58 (br s, 1H), 3.86 (s, 3H), 3.24-3.14 (m, 2H), 2.74 (dd, J=7.3, 7.0 Hz, 2H), 2.48 (s, 3H), 1.95-1.83 (m, 2H), 1.42 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With isopropylmagnesium bromide; In tetrahydrofuran; at 20℃; for 19h;Inert atmosphere; Cooling with ice; | Add dry THF (30mL) to the reaction flask,Then add SM 69 (2.5g, 10mmol), Under nitrogen protection, add 1N isopropyl magnesium bromide (10mL, 1M in THF) under ice-water bath conditions,Then react at room temperature for 7 hours, and finally add tert-butyl 5-oxopyrrolidine-1-carboxylate (1.85g, 10mmol),Then react at room temperature for 12 hours. The reaction solution was poured into saturated aqueous ammonium chloride solution, extracted with 30 mL (10 mL×3) ethyl acetate, and the organic phases were combined.After drying with anhydrous sodium sulfate and purifying by column chromatography, Int 340-1 (1.7 g, 5.6 mmol) was obtained with a yield of 56%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | General procedure: To a cooled -78 C solution of <strong>[19932-85-5]6-bromo-3H-1,3-benzoxazol-2-one</strong> (or 7-bromo-3H- 1,3-benzoxazol-2-one, 1.0 eq.) in anydrous THF (0.1 M) was added MeMgBr (1.5 eq., 3.0 M in Et2O). After 30 min, n-BuLi (4.5 eq., 2.5 M in hexanes) was added and the reaction mixture was stirred at -78 C for 30 min. A solution of appropriate ketone Va-b (2.4 eq.) or appropriate N- Boc lactam XXa-f (2.0- 5.0 eq), or appropriate Weinreb amide XXIa-b (2.0- 5.0 eq) in anhydrous THF (3.0 M) was then added dropwise at -78 C and the reaction mixture allowed to warm to RT. After 1h, the reaction mixture was quenched with saturated aq. NH4Cl solution and extracted with EA. The organic phase was washed with brine and dried over Na2SO4. After evaporation of the solvent, the residue was purified by column chromatography (SiO2), eluting with Cy/EA. |
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