Imidazole → (R)-2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethanol

HRID 2365790Notes

Reaction equation

N1C=CN=C1.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]([OH:16])[CH2:14][OH:15])=[CH:9][C:8]=1[F:17].[CH3:18][C:19]([Si:22](Cl)([CH3:24])[CH3:23])([CH3:21])[CH3:20]>C(Cl)Cl>[Si:22]([O:15][CH2:14][C@@H:13]([C:10]1[CH:11]=[CH:12][C:7]([Cl:6])=[C:8]([F:17])[CH:9]=1)[OH:16])([C:19]([CH3:21])([CH3:20])[CH3:18])([CH3:24])[CH3:23]

Participants

Conditions

Temperature: 0 °C

Procedure

Imidazole (13.1 g, 193 mmol) was added to a cold (0° C.) solution of (R)-1-(4-chloro-3-fluorophenyl)ethane-1,2-diol (14.7 g, 77.1 mmol) in DCM (100 mL), followed by TBSCl (12.8 g, 84.8 mmol). The reaction mixture was stirred at 0° C. for 1 hour and then quenched with water (50 mL). The layers were separated, and the organics were dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (100:1) to give (R)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanol (11.0 g, 47% over two steps). 1H NMR (400 MHz, CDCl3) δ 7.36 (m, 1H), 7.20 (m, 1H), 7.08 (m, 1H), 4.71 (m, 1H), 3.75 (m, 1H), 3.49 (m, 1H), 2.96 (d, J=2.6 Hz, 1H), 0.90 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H).

Workup

customquenched with water (50 mL)
customThe layers were separated
customthe organics were dried
filtrationfiltered
concentrationconcentrated
customThe crude product was purified via column chromatography
washeluting with hexanes/ethyl acetate (100:1)

Sources & evidence

ORD record: ord-3e590fc6ffaf444eb20e24d5ee77f6ac
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697715B2

Reaction notes

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