Isobutyl chloroformate → Methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate

Temperature

-10 °C

1-Methoxycarbonylcyclopropane carboxylic acid (16.4 g, 113.89 mmol), TEA (17.6 mL, 127.55 mmol), and THF (325 mL) are charged in a round bottom flask. The mixture is cooled to −10° C. and isobutyl chloroformate (16.5 mL, 127.55 mmol) is added dropwise. The solution is stirred for 1 h. In a separate flask, sodium borohydride (13 g, 341.67 mmol) is dissolved in a mixture of THF (165 mL) and water (40 mL) and cooled in an ice bath. The insoluble material is removed by filtration from the first solution. To the borohydride solution is added the 1-methoxycarbonylcyclopropane carboxylic acid solution described above, dropwise over a period of 1.5 h. The resulting solution is stirred at the same temperature for 1 h. The reaction mixture is poured into a cooled 20% aqueous solution of citric acid and extracted with ethyl acetate (3×150 mL). The combined organic layers are washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to afford the title compound (13.5 g, 91%). 1H NMR (400 MHz, CDCl3); δ 0.9-0.8 (m, 2H), 1.3-1.2 (m, 2H), 3.62 (s, 2H) 3.69 (s, 3H).

1. temperaturecooled in an ice bath
2. customThe insoluble material is removed by filtration from the first solution
3. additionTo the borohydride solution is added the 1-methoxycarbonylcyclopropane carboxylic acid solution
4. customof 1.5 h
5. stirringThe resulting solution is stirred at the same temperature for 1 h
6. additionThe reaction mixture is poured into a cooled 20% aqueous solution of citric acid
7. extractionextracted with ethyl acetate (3×150 mL)
8. washThe combined organic layers are washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure

ORD record

ord-5cc085d2d7a2418abf3b3e5285fba534

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288548B2