(Chief Bee)
03-02-03 18:24
No 413088
      Reduction of esters to alcohols w/ in situ LiBH4
(Rated as: excellent)

Below you'll find a high-yield reduction of N-Boc amino acids esters to N-Boc aminoalcohols with 2 equivalents of sodium borohydride/lithium chloride 1:1 in THF, which in situ forms the more powerful reducing agent lithium borohydride. Due to the insolubility of sodium chloride in THF, it precipitates and the reaction is forced to the right: NaBH4 + LiCl -> NaCl(s) + LiBH4(THF)
Naturally, the reduction works for all carboxylic acid esters, and also on free carboxylic acids to some extent.

An N-protected (Boc or Z) amino acids ester (0.25 mol) was dissolved in 350 ml THF under an inert atmosphere and anhydrous lithium chloride (21.2g, 0.5 mol) and then sodium borohydride (18.9g, 0.5 mol) were added. After addition of ethanol (700ml), the mixture was stirred at room temp overnight. The mixture was cooled with ice-water, adjusted to pH 4 by the gradual addition of 10% aqueous citric acid (ca 250 ml), and concentrated in vacuo. Water (700ml) was added to the residue, which was extracted with methylene chloride (3x600ml) and dried over sodium sulfate. Removal of the solvent gave the protected amino alcohol in 95% crude yield, and this could then be further purified by recrystallization or distillation.

Reference: JOC 52, 1252-1255 (1987)