Isopropyl Acetate → HCID 131731247, compound

Participants

Reaction Conditions

Reaction Steps

Crude A-2 (40 g assay; 55.94 g total) was dissolved in THF (773 mL). Ethanol (43.1 g) was added to the solution and the solution cooled to 0° C. LiBH4 (228 ml; 4.1M in THF) was added over 30 minutes at below 5° C. and mixture was stirred at RT. Mixture was warmed to 20° C. and stirred overnight. The reaction mixture was cooled to 10° C. and added 6M HCL (240 mL) with care over 30 minutes. The white cloudy mixture was stirred at 20° C. for 2 hours. pH of mixture: pH=1. The pH of the reaction mixture was adjusted to pH 12-14 by the addition of 10 M NaOH (120 mL) and isopropyl acetate (120 mL) added. The layers were separated and the aqueous layer re-extracted with isopropyl acetate (2×240 mL). The organic layers were combined and evaporated to residue. The oily residue was flushed with isopropanol (3×200 mL) to give a water content of <200 μL/mL. The crude oil was then dissolved in THF (450 mL). Solvent analysis gave no IPAc present, <1% IPA present. A solution of D-(+)-camphorsulfonic acid (54.3 g) in THF (130 mL) was added over 30 minutes to the THF solution of the piperidinol. A white solid crystallized. The mixture was stirred at 20° C. overnight. The slurry was diluted with MTBE (300 mL) and the mixture was cooled to 0° C. for 2 hours before filtering. The solid was washed with 1:1 THF:MTBE (100 mL) and MTBE (100 mL). The solid was dried in vacuo at 45° C. overnight to give A-5 as a white solid (39.7 g) in 47% yield, diastereomer ratio: 20:1 trans:cis (NMR)

Provenance & Evidence