Dimethyl Sulfoxide → (5S,6S)-5-Azido-6-(2,3-difluorophenyl)-5,6,7,8-tetrahydro-9H-cyclohepta[b]pyridin-9-one

HRID 589002Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[N:11]([C@@H:14]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[C@H:18]([OH:25])[CH2:17][CH2:16][C@H:15]1[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[F:33])=[N+:12]=[N-:13].C(N(CC)CC)C>ClCCl>[N:11]([C@@H:14]1[C:24]2[C:19](=[N:20][CH:21]=[CH:22][CH:23]=2)[C:18](=[O:25])[CH2:17][CH2:16][C@H:15]1[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[F:33])=[N+:12]=[N-:13]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of oxalyl chloride (0.22 mL, 2.6 mmol) in dichloromethane (20 mL) at −15° C. was added DMSO (0.24 mL, 3.4 mmol). The reaction mixture was cooled to −78° C. and a solution of (5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (prepared according to the procedures described in WO2011/046997, 270 mg, 0.85 mmol) in dichloromethane (5 mL) was added and the resulting solution was stirred at −78° C. for 2 h. Triethylamine (0.71 mL, 5.1 mmol) was added and the reaction mixture was allowed to warm to ambient temperature and then washed with water (15 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc 100:0 to 0:100, to give the title compound. MS: m/z=315.2 (M+1).

Workup

additionwas added
temperatureto warm to ambient temperature
washwashed with water (15 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography
washeluting with a gradient of hexanes:EtOAc 100:0 to 0:100

Sources & evidence

ORD record: ord-49ed655852884777a4c82d63e201b278
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227973B2

Reaction notes

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