ChemicalBook CAS DataBase List (1R,2R)-2-Methylcyclopropane-1-carboxylic acid

(1R,2R)-2-Methylcyclopropane-1-carboxylic acid synthesis

11synthesis methods

Product Name:(1R,2R)-2-Methylcyclopropane-1-carboxylic acid
CAS Number:10487-86-2
Molecular formula:C5H8O2
Molecular Weight:100.12

867-13-0
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$10.00/1g

16088-62-3 Synthesis

16088-62-3
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$21.00/1mL

(1R,2R)-2-Methylcyclopropane-1-carboxylic acid

10487-86-2
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$160.00/500mg

Yield: 92%

Reaction Conditions:

Stage #1:diethoxyphosphoryl-acetic acid ethyl ester with n-butyllithium in 2-methyltetrahydrofuran;hexane at 0; for 0.5 h;
Stage #2:(S)-Propylene oxide in 2-methyltetrahydrofuran;hexane at 150; for 18 h;sealed teflon lined steel reactor;
Stage #3: with water;sodium hydroxide in 2-methyltetrahydrofuran;hexane at 100; for 5 h;

Steps:

6.26
To a 0° C. solution of ethyl 2-(diethoxyphosphoryl)acetate (16.90 mL, 84.37 mmol) in methyltetrahydrofuran (150 mL) was added n-BuLi (33.0 mL, 82.5 mmol, 2.5 M in hexane). The reaction was maintained at 0° C. for 30 minutes before the addition of (S)-2-methyloxirane. The reaction mixture was then transferred to a teflon lined steel reactor, sealed and heated to 150° C. for 18 h. The reactor was cooled to room temperature, then treated with water:30% aq. NaOH (2:1) and refluxed at 100° C. for 5 h. The biphasic mixture was again cooled to room temperature and transferred to a separatory funnel. The layers were separated and the aqueous phase was acidified with conc. aq. HCl (100 mL) and extracted with isopropyl acetate (3×200 mL) while maintaining the aqueous phase at pH3. The combined organics were washed with 10% NaCl (2×100 mL), filtered over celite and concentrated to provide (1R,2R)-2-methylcyclopropanecarboxylic acid (7.9 g, 92% yield), which was used directly in the next reaction. ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.40-1.52 (m, 1H), 1.30-1.39 (m, 1H), 1.20-1.28 (m, 1H), 1.13 (d, J=6.0 Hz, 3H), 0.76 (ddd, J=7.8, 6.5, 4.0 Hz, 1H).

References:

Augeri, David John;Bagdanoff, Jeffrey Thomas;Baugh, Simon David Peter;Carlsen, Marianne;Carson, Kenneth Gordon;Gilleran, John Anthony;He, Wei;Oravecz, Tamas;Salojin, Konstantin;Sung, Leonard US2012/225857, 2012, A1 Location in patent:Page/Page column 19