Tetrahydrofuran → N-(3-Methylbutyl)-5-t-butyloxycarbonylamino 6-cyclohexyl-1-hexen-4-ol-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(3-methylbutyl)-2-methylpropenamide (643 mg, 4.15 mmol) in 25 ml of dry tetrahydrofuran was cooled under an N2 atmosphere to -78° C. and treated dropwise with 3.28 ml (8.5 mmol) of n-butyl-lithium in hexane. The resulting solution was warmed to 0° C. for 20 minutes, recooled to -78° C. and treated with 6.2 mL (6.2 mmol) of chlorotitanium triisopropoxide in hexane. After again warming to 0° C. for 5 minutes, the dark solution was recooled to -78° C. treated with a solution of N-t-butyloxycarbonylcyclohexylalaninal (670 mg, 2.3 mmol) in 5 ml of tetrahydrofuran, stirred for 5 minutes at -78° C., warmed to 0° C. for 20 minutes and quenched with saturated aqueous ammonium chloride. The resulting suspension was treated with ca. 50 ml of ether, stirred until the salts became white, extracted with two 100 ml portions of ether, dried over MgSO4 and concentrated in vacuo. The crude mixture was separated by flash column chromatography using 4:1 chloroform/ethyl acetate to give 249 mg (25%) of the (4S,5S) product (Rf 0.44), 292 mg (31%) of the (4R,5S) product (Rf 0.36, 3:2 chloroform/ethyl acetate) and 184 mg (20%) of a ca. 1:1 mixture of the two products. Mass spectrum: M+ =410.

Provenance & Evidence