Ammonia → [3-(Tert-butyl-dimethyl-silanyloxymethyl)-cyclohex-3-enyl]-acetaldehyde

Participants

Reaction Conditions

Reaction Steps

The benzyl protected alcohol (Intermediate A4) (2.0 g, 5.55 mmol) in THF (20 mL) was cooled to −70° C. and NH3 was condensed in this flask (˜20 mL). Na chunks were added and the mixture was allowed to stir at −70° C. for 15 m. The mixture was warmed to −30° C. for 20 m. The mixture was quenched with NH4Cl and the product was isolated by extraction. The residue was purified by chromatography on SiO2 with 25% EtOAc:Hx (99%). The alcohol was oxidized by the standard “Swern-type” protocol. A solution of oxalyl chloride (33 mL, 2M in CH2Cl2) (available from Aldrich) in CH2Cl2 was cooled to −78° C. DMSO (5.4 mL, 76 mmol) in CH2Cl2 (80 mL) was added via addition funnel over 45 m, and the mixture stirred for an addition 45 m. A solution of the alcohol, 2-[3-(tert-butyl-dimethyl-silanyloxymethyl)-cyclohex-3-enyl]-ethanol (13.7 g, 50.8 mmol) in CH2Cl2 (45 mL) was added over 30 m to this solution at −78° C. After 1 h, NEt3 (14.5 mL) in CH2Cl2 (10 mL) was added over 15 m and the mixture was warmed to rt for 3 h. After standard aqueous work-up and flash chromatographic purification, [3-(tert-butyl-dimethyl-silanyloxymethyl)-cyclohex-3-enyl]-acetaldehyde (Intermediate A5) was isolated 10 g (˜75%).

Provenance & Evidence