Ethyl Acetate → 2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

HRID 597907Notes

Reaction equation

HRID 597907 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:12]([CH3:13])[CH2:11][N:10](C(=O)C(F)(F)F)[CH2:9][CH2:8][C:7]=2[N:20]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O.C([O-])(O)=O.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:12]([CH3:13])[CH2:11][NH:10][CH2:9][CH2:8][C:7]=2[N:20]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 236541072-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

Product 1

HCID 236537272-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 2-methoxy-5-methylene-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (495 mg, 1.73 mmol), 10% Pd/C (60 mg) and MeOH (40 ml) was stirred under a H2 atmosphere (1 atm) for 2 h at ambient temperature. Filtration and concentration of the filtrate in vacuo gave 490 mg (98%) of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (DMSO-d6) δ 7.52 (d, 1H), 6.65 (m, 1H), 3.94-3.73 (m, 5H), 3.65-3.44 (m, 2H), 3.24-3.05 (m, 3H), 1.20 (m, 3H) ppm. A mixture of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (97.0 mg, 346 μmol) and K2CO3 (100 mg) in MeOH (10 ml) was heated at reflux for 2 h. The reaction mixture was parted between EtOAc and NaHCO3.The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. Chromatographic purification rendered 63 mg (95%) of 2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.35 (d, 1H), 6.51 (d, 1H), 3.90 (s, 3H), 3.10 (m, 2H), 3.04-2.93 (m, 4H), 2.75 (dd, 1H), 1.30 (d, 3H) ppm.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customChromatographic purification

Sources & evidence

ORD record
ord-ed64c163b3794c2f8879ea486a70ad65
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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