Ammonia → NMS-P118

HRID 333219Notes

Reaction equation

[F:1][C:2]1([F:27])[CH2:7][CH2:6][CH:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C:22](=[O:23])[C:21]4[C:20]([C:24]#[N:25])=[CH:19][C:18]([F:26])=[CH:17][C:16]=4[CH2:15]3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1.[OH2:28].N>C(O)(=O)C.S(=O)(=O)(O)O>[F:27][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([N:8]2[CH2:9][CH2:10][CH:11]([N:14]3[C:22](=[O:23])[C:21]4[C:20]([C:24]([NH2:25])=[O:28])=[CH:19][C:18]([F:26])=[CH:17][C:16]=4[CH2:15]3)[CH2:12][CH2:13]2)[CH2:4][CH2:3]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of [2-[1-(4,4-difluorocyclohexyl)-piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carbonitrile (1.44 g, 3.82 mmol) in acetic acid (11 mL), concentrated sulfuric acid (5.8 mL) was added dropwise during 30 min. The reaction was then warmed at 80° C. for 9 hours, cooled at room temperature and poured into cold water (20 mL). The aqueous phase was then made basic by adding concentrated aqueous ammonia and extracted with dichloromethane (3×10 mL). The combined organic phases were washed with 2N aqueous sodium hydroxide (2×12 mL) and brine, dried over sodium sulfate, and evaporated to dryness in vacuo. The title compound was obtained as a white solid (1 g, 67%) after purification through column chromatography, using dichloromethane/ethanol:95/5 as the mobile phase.

Workup

temperaturecooled at room temperature
extractionextracted with dichloromethane (3×10 mL)
washThe combined organic phases were washed with 2N aqueous sodium hydroxide (2×12 mL) and brine
dry with materialdried over sodium sulfate
customevaporated to dryness in vacuo

Sources & evidence

ORD record: ord-a81b51ceeeea4a5f816a427858fed338
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877944B2

Reaction notes

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