Formic Acid → 2-Formyl-17beta-estradiol

To a solution of chlorosulfonyl isocyanate (0.13 mL, 1.5 mmol) in CH2 Cl2 (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 1h. To a solution of 17β-tert-butyl-dimethylsilyloxy-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.

1. stirringThe reaction mixture was stirred for 1 h
2. additionthe pre-prepared reagent was added
3. stirringstirring
4. waitcontinued for 4 h at room temperature
5. customThe reaction mixture was quenched with saturated aqueous NH4Cl at 0° C.
6. extractionextracted with EtOAc
7. washThe combined organic layers were washed with H2O
8. dry with materialwith saturated aqueous NaCl, and dried (MgSO4)
9. filtrationThe desiccant was filtered
10. customthe solvent was evaporated at reduced pressure
11. customThe residue was purified by column chromatography (silica gel)

ORD record

ord-800f537aeff14c9fbe8dc09ef8a6295b

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05763432