Acetonitrile → Phenacyl bromide

Participants

Reaction Steps

The optically pure epoxide 1 is prepared from commercially available 4-benzyloxy-3-nitroacetophenone. Thus, the acetophenone may be brominated with bromine in an inert organic solvent such as CH3CN, MeOH or chloroform to give the α-bromoacetophenone. The bromoacetophenone is then reduced with a borane reducing agent such as BH3.THF or BH3.Me2S in the presence of a chiral oxazaborolidine catalyst to give the optically active bromohydrin by extraction from aqueous acid in excellent yield (>98%) and good enantiomeric excess (ee=95%). An example of such a catalyst is cis-(1R,2S)-aminoindanol-B-Me, or AIBMe, which is the product of the reaction between cis-(1R,2S)-aminoindanol and trimethylboroxine, according to the procedure described in U.S. Pat. No. 5,495,821. The bromohydrin can be further enriched to >99.8% ee by crystallization. The absolute configuration of the bromohydrin is determined by the chirality of the oxazaborolidine catalyst. The resulting compound is converted to optically pure 4-benzyloxy-3-nitrostyrene oxide with a base such as aq. NaOH or K2CO3 in an alcohol solvent or solvent mixture such as MeOH/THF. The epoxide can be isolated by extraction of the reaction mixture with ethyl acetate/water, drying the organic phase and evaporating the solvent.

Provenance & Evidence