Hydrochloric Acid → Methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate

Temperature

0 °C

A solution of cyclopropane-1,1-dicarboxylic acid methyl ester (9 g, 62.4 mmol) in THF (180 mL), is cooled to 0° C. and triethylamine (9.7 mL, 69.6 mmol) and 3-methyl-butyryl chloride (9.1 mL, 9.6 mmol) are added and the reaction stirred for 1 h. In a separate flask, sodium borohydride (7.1 g, 188 mmol) is dissolved in THF (100 mL)/H2O (25 mL) and cooled to 0° C. The mixed anhydride is filtered through a sintered funnel to remove salts from previous reaction and added to the flask containing sodium borohydride and the reaction stirred for 1 h at 0° C. 1 N HCl is added and the product is extracted with EtOAc and then with CCl3H/iPrOH. It is then purified via FCC eluting with Heptane/EtOAc (100:0 to 20:80) to give 1-hydroxymethyl-cyclopropanecarboxylic acid methyl ester. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.61 (t, J=5.81 Hz, 1H) 3.59 (s, 3H) 3.55 (d, J=6.06 Hz, 2H) 1.01 (d, J=3.03 Hz, 2H) 1.01 (d, J=10.36 Hz, 1H) 0.87 (d, J=3.03 Hz, 1H) 0.85-0.88 (m, 1H).

1. filtrationThe mixed anhydride is filtered through a sintered funnel
2. customto remove salts
3. customfrom previous reaction
4. additionadded to the flask
5. stirringthe reaction stirred for 1 h at 0° C
6. extractionthe product is extracted with EtOAc
7. customIt is then purified via FCC
8. washeluting with Heptane/EtOAc (100:0 to 20:80)

ORD record

ord-f6e0f86416b44e35ae15cc59bc242546

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501756B2