Ammonium Chloride → (4R,5S,6S)-1,1-diisopropoxy-5-hydroxy-2,2,4,6-tetramethyl-8-nonen-3-one

HRID 1357396Notes

Reaction equation

C([O:4][CH:5]([O:13][CH:14]([CH3:16])[CH3:15])[C:6]([CH3:12])([CH3:11])[C:7](=[O:10])[CH2:8][CH3:9])(C)C.C([N-][CH:21]([CH3:23])[CH3:22])(C)C.[Li+].[CH3:25][C@@H:26]([CH2:29][CH:30]=[CH2:31])[CH:27]=[O:28].[NH4+].[Cl-]>C1COCC1.C(Cl)Cl>[CH:14]([O:13][CH:5]([O:4][CH:21]([CH3:22])[CH3:23])[C:6]([CH3:11])([CH3:12])[C:7](=[O:10])[C@H:8]([CH3:9])[C@@H:27]([OH:28])[C@@H:26]([CH3:25])[CH2:29][CH:30]=[CH2:31])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 1,1-diisopropoxy-2,2,-dimethyl-3-pentanone (3.29 g) in 15 mL of THF is added slowly to a solution of lithium diisopropylamide (15.7 mmol) in 20 mL of THF cooled to −78° C., the mixture is stirred for 30 minutes, warmed to −40° C. and stirred for 30 minutes, then recooled to −78° C. A solution of (2S)-2-methyl-4-pentenal (16.36 mmol) in 2 mL of CH2Cl2 is added and the mixture is stirred for 1 hour at −78° C. Saturated aq. NH4Cl is added and the mixture is warmed to ambient temperature and extracted with ethyl acetate. The extract is dried over Na2SO4, filtered, and evaporated. The residue is purified by silica gel chromatography (2% ethyl acetate/hexanes) to separate the two diastereomeric products.

Workup

temperaturewarmed to −40° C.
stirringstirred for 30 minutes
customrecooled to −78° C
stirringthe mixture is stirred for 1 hour at −78° C
temperaturethe mixture is warmed to ambient temperature
extractionextracted with ethyl acetate
dry with materialThe extract is dried over Na2SO4
filtrationfiltered
customevaporated
customThe residue is purified by silica gel chromatography (2% ethyl acetate/hexanes)
customto separate the two diastereomeric products

Sources & evidence

ORD record: ord-20224d720c7849919f5323e36967a0a8
Source dataset: uspto-grants-2003_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06589968B2

Reaction notes

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