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

HRID 597932Notes

Reaction equation

HRID 597932 reaction equation
[CH3:1][O:2][C:3]1[C:4]([N+:21]([O-:23])=[O:22])=[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+].CO>O>[CH3:1][O:2][C:3]1[C:4]([N+:21]([O-:23])=[O:22])=[CH:5][C:6]2[CH:12]([CH3:13])[CH2:11][NH:10][CH2:9][CH2:8][C:7]=2[N:20]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 236542852-methoxy-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

Product 1

HCID 236539062-methoxy-5-methyl-3-nitro-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepineYield 99%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Nitric Acid (200 μl) was added dropwise to a stirred solution of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (174 mg, 604 μmol) in H2SO4 (1.5 ml). The reaction mixture was added into cold water after 3 d of stirring at room temperature. K2CO3 was added to neutralize the mixture to pH=8. After extraction with EtOAc, the organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 155 mg (77%) of 2-methoxy-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. MS (ESI) m/z 334. After treatment of 2-methoxy-5-methyl-3-nitro-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (30.0 mg, 90.0 μmol) with K2CO3 (30 mg), methanol (1 ml) and H2O (0.2 ml) at 60° C. for 10 minutes, the reaction was quenched with sat. aq. NH4Cl and extracted with DCM. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 21 mg (99%) of 2-methoxy-5-methyl-3-nitro-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 8.10 (s, 1H), 4.09 (s, 3H), 3.25 (m, 2H), 3.10 (m, 3H), 2.93 (dd, 1H), 2.72 (dd, 1H), 1.39 (d, 3H) ppm.

Workup

  1. customthe reaction was quenched with sat. aq. NH4Cl
  2. extractionextracted with DCM
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-9775c42973e1407b80f14f00c6dcfbd3
Source dataset
uspto-grants-2011_03
Patent number
US07897595B2

Reaction notes

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