Lithium borohydride → Boc-His(Ts) 3-cyclohexyl-alaninol

Participants

Reaction Steps

The extract is dried over MgSO4 and evaporated to dryness in vacuo to quantitatively obtain 3-cyclohexylalanine methyl ester [16a] as an oil. The product is then, without further purification, dissolved in dichloromethane (50 ml). To the solution are added Boc-His(Ts).DCHA [8a](10.7 g, 18.11 mmol, 1.3 eq) and diethyl cyanophosphonate (2.95 g, 18.1 mmol, 1.3 eq), and the mixture is stirred for 1.5 hours at room temperature. The reaction mixture is subjected to silica gel chromatography (SiO2 :300 g, CH2Cl2 :MeOH=99:1) to give a purified Boc-His(Ts)-3-cyclohexylalanine methyl ester [17a] (7.43 g, 93%) as an oil. To a solution of the dipeptide ester [17a](3.0 g, 5.2mmol) in THF (6 ml) and ethanol (6 ml) is added a 2N solution of lithium borohydride in THF (3 ml, 6 mmol) with stirring and ice-cooling. After 20 minutes stirring, the mixture is allowed to react at room temperature for additional one hour. The solvent is removed in vacuo and the residue added ice water and saturated aqueous ammonium chloride is extracted with dichloromethane (20 ml×3). The organic layer is washed with saturated aqueous sodium chloride, dried over MgSO4, evaporated to dryness in vacuo and the residue is purified by silica gel chromatography (SiO2 : 200 g, CH2Cl2 :MeOH=98:2) to obtain Boc-His(Ts)-3-cyclohexyl-alaninol [18a] (2.06 g, 72%) as an oil.

Provenance & Evidence