Imidazole → HCID 67182450, compound

HRID 1026164Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:16])([O:10][CH2:11][C@@H:12]([OH:15])[CH2:13][OH:14])[CH3:9])=[CH:4][CH:3]=1.N1C=CN=C1.[C:22]([Si:26](Cl)([CH3:28])[CH3:27])([CH3:25])([CH3:24])[CH3:23].O>O1CCCC1.CN(C)C1C=CN=CC=1>[C:22]([Si:26]([CH3:28])([CH3:27])[O:14][CH2:13][C@H:12]([OH:15])[CH2:11][O:10][C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)([CH3:16])[CH3:9])([CH3:25])([CH3:24])[CH3:23]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (S)-3-[1-(4-fluoro-phenyl)-1-methyl-ethoxy]-propane-1,2-diol (0.46 g) in tetrahydrofuran (6 ml) were added imidazole (0.32 g) and 4-dimethylaminopyridine (catalytic amount). The mixture was cooled to 0° C. and a solution of tert-butyl(chloro)dimethylsilane (0.32 g) in tetrahydrofuran (2 ml) was added dropwise. After 2 hours at 0° C., the reaction mixture was allowed to stir at room temperature for 16 hours. Water was added and the mixture was extracted twice with diethylether. The combined organic layers were dried (MgSO4) and evaporated. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 90:10->75:25) to give (R)-1-(tert-butyl-dimethyl-silanyloxy)-3-[1-(4-fluorophenyl)-1-methyl-ethoxy]-propan-2-ol (0.57 g, 83%) as a colorless liquid. 1H NMR (300 MHz, CDCl3, δ): 0.00 (s, 6H), 0.82 (s, 9H), 1.48 (s, 6H), 2.49 (bs, 1H), 3.15 (d, J=4 Hz, 2H), 3.56 (t, J=4 Hz, 2H), 3.68 (m, 1H)

Workup

extractionthe mixture was extracted twice with diethylether
dry with materialThe combined organic layers were dried (MgSO4)
customevaporated
customThe crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 90:10->75:25)

Sources & evidence

ORD record: ord-4d1e4d3d328b489099d74b85240bd46e
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729113B2

Reaction notes

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