Sodium Hydroxide → 8'-Azaspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,3'-bicyclo[3.2.1]octane]

HRID 1907995Notes

Reaction equation

FC(F)(F)C([N:5]1[CH:10]2[CH2:11][CH2:12][CH:6]1[CH2:7][C:8]1([O:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[N:14]3[CH:22]=[CH:23][CH:24]=[C:13]13)[CH2:9]2)=O.[OH-].[Na+]>CO>[CH:6]12[NH:5][CH:10]([CH2:11][CH2:12]1)[CH2:9][C:8]1([O:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[N:14]3[CH:22]=[CH:23][CH:24]=[C:13]13)[CH2:7]2

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2: 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 (469 mg, 1.29 mmol) in MeOH (5 mL) was added NaOH (1.3 mL of 2.0 M, 2.6 mmol). The solution was heated at 70° C. overnight. The reaction was then cooled to room temperature and the organics were extracted with EtOAc (3×100 mL), combined, and dried over Na2SO4. The organic layer was then filtered and concentrated to provide 8′-azaspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,3′-bicyclo[3.2.1]octane] as an opaque oil in quantitative yield. 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J=7.7 Hz, 1H), 7.09-6.96 (m, 4H), 6.26 (t, J=3.2 Hz, 1H), 5.97 (d, J=3.4 Hz, 1H), 3.58 (s, 2H), 2.40-2.29 (m, 2H), 2.21-2.15 (m, 2H), 2.09 (dd, J=15.0, 3.1 Hz, 2H), 1.86-1.77 (m, 2H). ESI-MS m/z calc. 266.3. found 267.3 (M+1)+; Retention time: 1.04 minutes (3 min run).

Workup

temperatureThe reaction was then cooled to room temperature
extractionthe organics were extracted with EtOAc (3×100 mL)
dry with materialdried over Na2SO4
filtrationThe organic layer was then filtered
concentrationconcentrated

Sources & evidence

ORD record: ord-19b98f54cc5d4534a2a382e96bb870c7
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598164B2

Reaction notes

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