Methanol → 2-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

HRID 597927Notes

Reaction equation

HRID 597927 reaction equation
[F:1][CH:2]([F:22])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH:13]([CH3:14])[CH2:12][N:11](C(=O)C(F)(F)F)[CH2:10][CH2:9][C:8]=2[N:21]=1.C([O-])([O-])=O.[K+].[K+].CO>O>[F:22][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[CH:13]([CH3:14])[CH2:12][NH:11][CH2:10][CH2:9][C:8]=2[N:21]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 86616698HCID 86616698, compound

Product 1

HCID 236539042-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepineYield 36%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (77.0 mg, 281 μmol), K2CO3 (19.0 mg, 141 μmol) and DMF (1.4 ml) was added F2ClCCO2Na (47.0 mg, 310 μmol). The mixture was heated at 90° C. for 2 h. The reaction mixture was parted between sat. aq. NaHCO3 and EtOAc. The organic layer was dried, concentrated in vacuo and purified by means of column chromatography to give 49.0 mg (54%) of 2-(difluoromethoxy)-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. MS (ESI) m/z 325.2. A mixture of 2-(difluoromethoxy)-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (28.0 mg, 86.0 μmol), K2CO3 (30 mg), MeOH (1 ml) and H2O (200 μl) was heated to reflux for 10 min. The reaction mixture was concentrated in vacuo and the resulting residue was purified by column chromatography to yield 7.0 mg (36%) of 2-(difluoromethoxy)-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.46 (d, 1H), 6.66 (d, 1H), 3.09 (m, 2H), 3.40-2.90 (m, 4H), 2.74, (dd, 1H), 1.31 (d, 3H) ppm.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 10 min
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-009c42a338a143a2b508dcc63afe4d21
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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