Methanol → Methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate

Temperature

0 °C

1,1-Cyclopropane dicarboxylic acid-1-methyl ester (4 g, 27.8 mmol) was mixed with DIPEA (6 ml, 34.4 mmol) in THF (50 ml) and stirred at a 0° C. for 10 min. To the reaction was slowly added ethyl chloroformate (2.7 ml, 28.1 mmol). The reaction was stirred for 1.5 hours and allowed to warm to ambient temperature. The reaction was then re-cooled to 0° C. and NaBH4 (1.6 g, 42.3 mmol) was slowly added, followed by the addition of methanol (3 ml, 74.2 mmol). The reaction was allowed to warm to ambient temperature over 2 h. Then the reaction was diluted with EtOAc and water. The aqueous layer was separated and extracted with EtOAc three times. The combined organic layers were washed with water, then brine, dried over (MgSO4), filtered, and concentrated to afford the title compound. 1H NMR (500 MHz, CDCl3): δ 3.70 (s, 3H), 3.60 (s, 2H), 1.25 (m, 2H), 0.85 (m, 2H).

1. stirringThe reaction was stirred for 1.5 hours
2. temperatureto warm to ambient temperature
3. temperatureThe reaction was then re-cooled to 0° C.
4. temperatureto warm to ambient temperature over 2 h
5. customThe aqueous layer was separated
6. extractionextracted with EtOAc three times
7. washThe combined organic layers were washed with water
8. dry with materialbrine, dried over (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-37f2b2f235234ec6aea3eb12b6799e9a

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895596B2