Formic Acid → 2-Formyl-17beta-estradiol

Participants

Reaction Steps

To a solution of chlorosulfonyl isocyanate (0.13 mL, 1.5 mmol) in CH2Cl2 (1.0 mL) was added formic acid (0.31 mL of a CH2Cl2 solution, 5.0M, 1.6 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 1 h. To a solution of 17β-tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-triene-2-carbox aldehyde (9, 0.129 g, 0.31 mmol) in DMF (3.0 mL) was added sodium hydride (0.044 g of a mineral oil dispersion, 60%, 1.1 mmol) at 0° C. The reaction mixture was stirred for 1 h, the pre-prepared reagent was added, and stirring continued for 4 h at room temperature. The reaction mixture was quenched with saturated aqueous NH4Cl at 0° C. and extracted with EtOAc. The combined organic layers were washed with H2O, then with saturated aqueous NaCl, and dried (MgSO4). The desiccant was filtered and the solvent was evaporated at reduced pressure. The residue was purified by column chromatography (silica gel) using n-hexane:acetone (2:1→1:1, v/v) to afford 0.017 g of 2a (18% yield) and 0.030 g of 10 (27% yield), m.p. 170°-172° C.

Provenance & Evidence