Sodium hydride → HCID 59396023, compound

Participants

Reaction Conditions

Reaction Steps

To an ice cooled solution of phenylmethyl ((1S)-2-{[(1,1 dimethylethyl)(diphenyl)silyl]oxy}-1-{[2-(hydroxymethyl)cyclopropyl]methyl}ethyl)carbamate single diastereoisomer 1 D7 (1.18 g) in DCM (35 ml) and TEA (0.953 ml, 6.84 mmol) was added mesyl chloride (0.355 ml, 4.56 mmol) and the resulting mixture was stirred for 3 hours. After this time the solvent was removed under reduced pressure and the white solid obtained was dissolved in DMF (47 ml), the solution was cooled to 0° C. and NaH (0.730 g, 18.25 mmol, 8 eq) was added and ice bath was removed. After stirring overnight more NaH (0.365 g, 9.12 mmol, 4 eq) was added to the ice cooled mixture and stirred at room temperature for 3 hours. UPLC showed starting material and desired product in 1:1 ratio, so NaH (0.180 g, 4.5 mmol, 1.97 eq) was added at room temperature and stirred for 2.5 hours. A saturated solution of NH4Cl (300 ml) was added and extracted with EtOAc (3×50 mls), the organic phase was separated, dried (Na2SO4), filtered and evaporated to give a yellow oil which was purified via Biotage SP4 (silica gel, SNAP 100 g column; eluted with a gradient of Cy/EtOAc from 1/0 to 9/1). Collected fractions gave the title compound D8 (0.930 g) as a colourless oil. MS: (ES/+) m/z: 500 (M+1). C31H37NO3Si requires 499. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.76-7.31 (m, 15 H), 5.16-4.84 (m, 2 H), 4.37 (br.s, 1 H), 3.83-3.68 (m, 1 H), 3.68-3.52 (m, 2 H), 2.37-2.22 (m, 2 H), 1.39-1.18 (m, 1 H), 1.13-1.01 (m, 1 H), 0.95 (s, 9 H), 0.92-0.83 (m, 1 H), 0.79-0.70 (m, 1 H), 0.33-0.04 (m, 1 H).

Provenance & Evidence