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

Temperature

0 °C

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-butyloxycarbonyl-cyclohexylalaninal (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.

1. customrecooled to -78° C.
2. temperatureAfter again warming to 0° C. for 5 minutes
3. customwas recooled to -78° C.
4. temperaturewarmed to 0° C. for 20 minutes
5. customquenched with saturated aqueous ammonium chloride
6. additionThe resulting suspension was treated with ca. 50 ml of ether
7. stirringstirred until the salts
8. extractionextracted with two 100 ml portions of ether
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo
11. customThe crude mixture was separated by flash column chromatography
12. customto give

ORD record

ord-bfd223ee5835412e995e51a4c13a18de

Source dataset

uspto-grants-1991_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05059589