Imidazole → HCID 22852539, compound

HRID 1654216Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([C@H:12]([O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)[CH3:13])[CH2:11][O:10]1.[NH:21]1[CH:25]=[CH:24][N:23]=[CH:22]1.[H-].[Na+].O>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:10])([C@H:12]([O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1)[CH3:13])[CH2:11][N:21]1[CH:25]=[CH:24][N:23]=[CH:22]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2-(2,4-difluorophenyl)-2-[(1R)-1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]oxirane (1.7 g) and imidazole (0.49 g) in N,N-dimethylformamide (17 ml) was added 60% oily sodium hydride in mineral oil (0.29 g) by portions at 20° C. with constant stirring. After 5 minutes, the mixture was heated at 70° C. for 3 hours. The reaction mixture was cooled, then poured into water (50 ml) and extracted with ethyl acetate (20 ml×3). The ethyl acetate layers were combined, washed with saturated aqueous sodium chloride solution (20 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (3 cm×15 cm) using methanol-ethyl acetate (5:95) as the eluent. The desired fraction was concentrated under reduced pressure to give (3R)-2-(2,4-difluorophenyl)-1-(1-imidazolyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)-2-butanol (1.8 g) as a colorless syrup.

Workup

temperatureThe reaction mixture was cooled
extractionextracted with ethyl acetate (20 ml×3)
washwashed with saturated aqueous sodium chloride solution (20 ml)
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
concentrationThe desired fraction was concentrated under reduced pressure

Sources & evidence

ORD record: ord-e14f55ae4f294dfab0e7fe68c28171e8
Source dataset: uspto-grants-1995_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05405861

Reaction notes

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