tert-butyl N-[[1-(hydroxymethyl)cyclopropyl]methyl]carbamate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere 1-(tert-Butoxycarbonylamino-methyl)-cyclopropanecarboxylic acid (3.23 g, 15.0 mmol) was dissolved in THF (50 mL) and cooled to −70 C. Borane tetrahydrofurane complex (1 M in THF, 22.5 mL, 22.5 mmol) was added at −70 C. The mixture was then stirred at 0 C for 2.5 h after which borane tetrahydrofurane complex (1 M in THF, 7.5 mL, 7.5 mmol) was added at 0 C. The mixture was stirred at RT for 1.5 h. Aq. NH4Cl (50 mL) was added at 20 C and the aqueous phase was extracted with EtOAc (×3). The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo to afford (1-Hydroxymethyl-cyclopropylmethyl)-carbamic acid tert-butyl ester (2.6 g) as an oil. cooled to −70 C was added at 0 C the aqueous phase was extracted with EtOAc (×3) The combined organic phases were dried over Na2SO4 filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere oxalyl chloride (1.17 mL, 13.8 mmol) was dissolved in DCM (30 mL) and cooled to −70 C. DMSO (1.95 mL, 27.6 mmol) in DCM (2.5 mL) was added over 5 min and stirred for 10 min. (1-Hydroxymethyl-cyclopropylmethyl)-carbamic acid tert-butyl ester (2.6 g, 12 mmol) in DCM (8.5 mL) was added at −70 C over 5 min and the mixture was stirred for 30 min. Et3N (6.4 mL, 45.6 mmol) was added over 5 min and the temperature was allowed to reach RT over 1 h. H2O was added and the aqueous phase was extracted with DCM (×2). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica using heptane:EtOAc 1:15 as eluent to afford (1-Formyl-cyclopropylmethyl)-carbamic acid tert-butyl ester (0.65 g) as an oil. cooled to −70 C was added at −70 C over 5 min to reach RT over 1 h the aqueous phase was extracted with DCM (×2) The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated in vacuo The crude product was purified by flash chromatography on silica