Acetic Acid → 1-Methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]

HRID 2204071Notes

Reaction equation

HRID 2204071 reaction equation
C(O[CH2:5][C:6]1[N:10]2[C:11]3[CH:30]=[CH:29][CH:28]=[CH:27][C:12]=3[O:13][C:14]3([CH2:19][CH2:18][N:17](CC4C=CC=CC=4)[CH2:16][CH2:15]3)[C:9]2=[CH:8][CH:7]=1)(=O)C.C(O)(=O)C>C(OCC)(=O)C.[Pd]>[CH3:5][C:6]1[N:10]2[C:11]3[CH:30]=[CH:29][CH:28]=[CH:27][C:12]=3[O:13][C:14]3([CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)[C:9]2=[CH:8][CH:7]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 58551252(1'-Benzylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1-yl)methyl acetate

Product 1

HCID 585507081-Methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]Yield 34.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1′-benzylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-yl)methyl acetate (300 mg, 0.75 mmol) in ethyl acetate (30 mL) was added acetic acid (17 μL, 0.30 mmol). The reaction was flushed with nitrogen then 10% Pd/C (40 mg, 0.37 mmol) was added. The reaction was placed under hydrogen gas and was stirred for 20 h at room temperature. The suspension was filtered through celite, concentrated, then purified by column chromatography (silica gel: 0.1-15% methanol in dichloromethane) to give 1-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine] (65 mg, 34%). ESI-MS m/z calc. 254.3, found 255.3 (M+1)+; Retention time: 1.93 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J=7.9 Hz, 1H), 7.16-6.99 (m, 3H), 6.03 (d, J=3.2 Hz, 1H), 5.94 (d, J=3.4 Hz, 1H), 3.14 (t, J=12.2 Hz, 2H), 2.94 (d, J=12.3 Hz, 2H), 2.56 (s, 3H), 2.19 (m, 1H), 2.04 (d, J=12.7 Hz, 2H), 1.97-1.84 (m, 2H).

Workup

  1. customThe reaction was flushed with nitrogen
  2. filtrationThe suspension was filtered through celite
  3. concentrationconcentrated
  4. custompurified by column chromatography (silica gel: 0.1-15% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e450779eee834a168e08ce2b50c808d5
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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