Trifluoroacetic acid → 2,2,2-Trifluoro-1-(8'-azaspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,3'-bicyclo[3.2.1]octane]-8'-yl)ethanone

HRID 2204080Notes

Reaction equation

C(O)(C(F)(F)F)=O.[N:8]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[CH:12]=[CH:11][CH:10]=[CH:9]1.[F:20][C:21]([F:34])([F:33])[C:22]([N:24]1[C@H:29]2[CH2:30][CH2:31][C@@H:25]1[CH2:26][C:27](=O)[CH2:28]2)=[O:23]>ClC(Cl)C>[F:34][C:21]([F:20])([F:33])[C:22]([N:24]1[CH:29]2[CH2:30][CH2:31][CH:25]1[CH2:26][C:27]1([O:19][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[N:8]3[CH:9]=[CH:10][CH:11]=[C:12]13)[CH2:28]2)=[O:23]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of TFA (387 μL, 5.02 mmol) in dichloroethane (18 mL) was added to 2-pyrrol-1-ylphenol (401 mg, 2.52 mmol) and (1R,5S)-8-(2,2,2-trifluoroacetyl)-8-azabicyclo[3.2.1]octan-3-one (620 mg, 2.80 mmol). The solution was heated at 70° C. overnight. The solvent was evaporated and the crude residue was purified by column chromatography (silica gel: 0-10% EtOAc in hexanes) to afford 2,2,2-trifluoro-1-(8′-azaspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,3′-bicyclo[3.2.1]octane]-8′-yl)ethanone as a clear oil (469 mg, 46%). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J=7.5 Hz, 1H), 7.07-6.94 (m, 4H), 6.23 (t, J=3.2 Hz, 1H), 5.87 (d, J=3.4 Hz, 1H), 4.74 (d, J=7.4 Hz, 1H), 4.42 (s, 1H), 2.50-2.34 (m, 2H), 2.34-2.16 (m, 3H), 2.16-1.89 (m, 3H). ESI-MS m/z calc. 362.4, found 363.3 (M+1)+; Retention time: 2.07 minutes (3 min run).

Workup

customThe solvent was evaporated
customthe crude residue was purified by column chromatography (silica gel: 0-10% EtOAc in hexanes)

Sources & evidence

ORD record: ord-ade4928340b043ca8383c0a9026de819
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365588B2

Reaction notes

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