4-Methylmorpholine → Ethyl (1R,2R)-2-(hydroxymethyl)cyclopropanecarboxylate

Temperature

-50 °C

Add isobutylchloroformate (0.41 mL, 3.16 mmol) and N-methylmorpholine (0.35 mL, 3.16 mmol) to a solution of (+/−)-trans-cyclopropane-1,2-dicarboxylic acid monoethyl ester (0.50 g, 3.161 mmol) in tetrahydrofuran (21 mL) at −50° C. Stir for 5 minutes and then filter into a slurry of sodium borohydride (0.084 g, 2.21 mmol) in tetrahydrofuran (9 mL) and cool to −50° C. Warm to room temperature over night and then add 9 mL of water. Remove tetrahydrofuran under reduced pressure and extract aqueous layer with diethyl ether (3×20 mL). Wash combined organic layers with saturated aqueous sodium chloride and dry over magnesium sulfate. Concentrate under reduced pressure and subject residue to silica gel chromatography eluting with 25-65% ethyl acetate in hexanes to provide the desired compound (0.224 g, 49.1%).

1. temperatureWarm to room temperature over night
2. extractionRemove tetrahydrofuran under reduced pressure and extract aqueous layer with diethyl ether (3×20 mL)
3. washWash
4. dry with materialdry over magnesium sulfate
5. concentrationConcentrate under reduced pressure
6. washeluting with 25-65% ethyl acetate in hexanes

ORD record

ord-87100962ed80480ebc2333cac2203e2e

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07745438B2