Hydrochloric Acid → HCID 69963137, compound

Participants

Reaction Steps

The mixture obtained from the above reaction, comprising (R)-1-(2,3-difluoro-6-nitrophenoxy)-2-trimethylsiloxypropane (1) and (S)-2-(2,3-difluoro-6-nitrophenoxy)-1-trimethylsiloxypropane (2), was dissolved in 200 mL of 10:1 CH2Cl2/MeOH at 0° C., and was treated with 5 mL of IM HCl in MeOH with stirring. The cooling bath was removed, and the mixture was aged for 30 minutes. The product mixture, which included (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol formed by the desilylation of 1 and (S)-2-(2,3-difluoro-6-nitrophenoxy)-propane-1-ol formed by the desilylation of 2, was concentrated to a yellow oil, which was dried under high vacuum to remove the solvent. After concentration, the residue was dissolved in dichloromethane, and triphenylmethyl chloride (trityl chloride, 4 equivalents based on the undesired alcohol regioisomer (S)-2-(2,3-difluoro-6-nitrophenoxy)propane-1-ol) was added, followed by pyridine (1 equivalent based on the triphenylmethyl chloride). The mixture was stirred at ambient temperature, and the progress of the reaction was followed by gas chromatographic analysis. When the product regioisomer ratio, i.e., the ratio of (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol to the triphenylmeythylated (S)-2-(2,3-difluoro-6-nitrophenoxy)propane-1-ol reached >100:<1, the reaction was concentrated to dryness. The oily residue was then purified by distillation as before, using a wiped film evaporator. The compound that distilled was (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol, which is the desilylated alcohol derived from 1. The triphenylmeythylated (S)-2-(2,3-difluoro-6-nitrophenoxy)propane-1-ol, i.e., (S)-2-(2,3-difluoro-6-nitrophenoxy)-1-triphenylmethyloxypropane did not distill. The overall yield for the three steps to produce (R)-1-(2,3-difluoro-6-nitrophenoxy)propan-2-ol was 90-95% based upon 2,3-difluoro-6-nitrophenol.

Provenance & Evidence