Acetic Acid → 1,1-Dimethylethyl N-[(2R,3S)-2-(2,5-difluorophenyl)tetrahydro-5-oxo-2H-pyran-3-yl]carbamate

HRID 711309Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To 46.8 kg (142 mol) of tert-butyl [(2R,3S)-2-(2,5-difluorophenyl)-5-hydroxytetrahydro-2H-pyran-3-yl]carbamate in a stirred vessel was added acetonitrile (150 kg), acetic acid (50 kg), and water (25 kg). After dissolving at room temperature, the solution was cooled to 0° C. and RuCl3.3H2O (250 g, 956 mmol) in water (50 kg) was added under nitrogen. Then, NaBrO3 (11.7 kg, 77.5 mol) was added in six portions every 1.5 h under nitrogen. After stirring at 0° C. for 6 h, 2-propanol (31 kg) was added over 30 min. at 0° C. Then, water (720 kg) was added at this temperature over 5 h. The resulting slurry was stirred overnight, filtered, and cake washed with water. The solids were then dried under vacuum at 40-60° C. to give tert-butyl [(2R,3S)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-pyran-3-yl]carbamate.

Workup

dissolutionAfter dissolving at room temperature
stirringThe resulting slurry was stirred overnight
filtrationfiltered
washcake washed with water
customThe solids were then dried under vacuum at 40-60° C.

Sources & evidence

ORD record: ord-5460b42a0d3d44899ee667f89be1fd57
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181262B2

Reaction notes

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