Hexane → α-[3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]phenyl]-2-thiazolemethanol

HRID 2258349Notes

Reaction equation

C([Li])CCC.CCCCCC.Br[C:13]1[S:14][CH:15]=[CH:16][N:17]=1.[Si:18]([O:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=1)[CH:29]=[O:30])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C(OCC)C.C(OCC)(=O)C>[S:14]1[CH:15]=[CH:16][N:17]=[C:13]1[CH:29]([OH:30])[C:28]1[CH:31]=[CH:32][CH:33]=[C:26]([O:25][Si:18]([C:21]([CH3:23])([CH3:22])[CH3:24])([CH3:20])[CH3:19])[CH:27]=1

Participants

Conditions

Temperature: -40 °C

Procedure

A solution of 1.6M n-butyllithium in hexane (206 mL, 0.33 mol) was cooled to -45° C. under nitrogen. A slurry of 2-bromothiazole (50 g, 0.30 mol) in 75 mL of diethyl ether was added in portions, maintaining a temp between -35° C. and -45° C. The resulting dark brown solution was stirred an additional 15 minutes at -40° C. before adding 3-(tert-butyldimethylsilyloxy)benzaldehyde (70.9 g, 0.30 mol, Example 54, infra) dropwise via syringe at a rate to maintain temperature between -25° C. and -35° C. The resulting mixture was stirred an additional 30 minutes at -15° C., then poured into a mixture of 1 L ice/600 mL 1M HCl. The organic phase was dried over sodium sulfate, and evaporated to give a brown oil. Chromatography on silica gel with hexane:ethyl acetate (gradient from 90:10 to 80:20) gave 25.5 g (26.4%) of a-(2-thiazolyl)-3-((tert-butyldimethyl-silyl)oxy)benzyl alcohol as a viscous yellow oil.

Workup

temperaturemaintaining a temp between -35° C. and -45° C
temperatureto maintain temperature between -25° C. and -35° C
stirringThe resulting mixture was stirred an additional 30 minutes at -15° C.
dry with materialThe organic phase was dried over sodium sulfate
customevaporated
customto give a brown oil

Sources & evidence

ORD record: ord-6c458f5a97e64545997055b35aa4667f
Source dataset: uspto-grants-1997_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05658908

Reaction notes

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