Pyridine, hydrofluoride (1:1) → 6-(2,3-Difluorophenyl)-5-fluoro-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

HRID 589007Notes

Reaction equation

F.N1C=CC=CC=1.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[CH:16]1[CH2:26][CH2:25][CH:24]([O:27][Si](C(C)C)(C(C)C)C(C)C)[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]1[F:38]>O1CCCC1>[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[CH:16]1[CH2:26][CH2:25][CH:24]([OH:27])[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]1[F:38]

Participants

Conditions

Temperature: 0 °C

Procedure

Pyridine hydrofluoride (0.037 g, 0.38 mmol) was added dropwise to a solution of (5R,6S,9R and 5S,6R,9S)-6-(2,3-difluorophenyl)-5-fluoro-9-((triisopropylsilyl)oxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine (0.155 g, 0.345 mmol) in tetrahydrofuran (3 mL) cooled to 0° C., and the mixture was stirred for 3 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (3×). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash chromatography on silica gel, eluting with 55% dichloromethane in petroleum ether to give the title compound as a racemic mixture. MS: m/z=294.2 (M+1).

Workup

customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (3×)
washThe combined organic layers were washed with brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated
customThe residue was purified by flash chromatography on silica gel
washeluting with 55% dichloromethane in petroleum ether

Sources & evidence

ORD record: ord-b1ec48dadab04392ac235c59ae858c4f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227973B2

Reaction notes

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