Potassium Nitrate → 8-Methoxy-2-methyl-7-nitro-2,3,4,5-tetrahydro-benzo[c]azepin-1-one

HRID 1686951Notes

Reaction equation

HRID 1686951 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH2:12][CH2:11][CH2:10][N:9]([CH3:13])[C:8](=[O:14])[C:7]=2[CH:15]=1.[N+:16]([O-])([O-:18])=[O:17].[K+]>CC#N.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.O>[CH3:1][O:2][C:3]1[C:4]([N+:16]([O-:18])=[O:17])=[CH:5][C:6]2[CH2:12][CH2:11][CH2:10][N:9]([CH3:13])[C:8](=[O:14])[C:7]=2[CH:15]=1

Participants

5

Reactant 2

HCID 24434Potassium NitrateHCID 672645628-Methoxy-2-methyl-2,3,4,5-tetrahydro-benzo[c]azepin-1-one

Product 1

HCID 672643708-Methoxy-2-methyl-7-nitro-2,3,4,5-tetrahydro-benzo[c]azepin-1-oneYield 14.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 86633852MeCN TFAASolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 8-Methoxy-2-methyl-2,3,4,5-tetrahydro-benzo[c]azepin-1-one (227 mgs, 1.1 mmol) in MeCN/TFAA (1:1, 2 mL) was cooled to 0° C. and treated with potassium nitrate (123 mg, 1.2 mmol), then warmed to room temperature and stirred for 2 h. Poured mixture in water, extracted (EtOAc), washed with brine and the organic layer dried (MgSO4), filtered and concentrated. ISCO purification (0 to 100% EtOAc/hexane, 40 g SiO2 column) provided 8-Methoxy-2-methyl-7-nitro-2,3,4,5-tetrahydro-benzo[c]azepin-1-one (40 mgs). 1H-NMR (CDCl3) δ δ 7.63 (s, 1H), 7.41 (s, 1H), 3.98 (s, 3H), 3.24 (t, J=6.3 Hz, 2H), 3.19 (s, 3H), 2.78 (t, J=7.1 Hz, 2H), 2.10-2.04 (m, 2H); LC/MS (ESI+): 250.98 (M+H). The regioisomer 8-Methoxy-2-methyl-9-nitro-2,3,4,5-tetrahydro-benzo[c]azepin-1-one was also isolated as a mixture with 8-Methoxy-2-methyl-7-nitro-2,3,4,5-tetrahydro-benzo[c]azepin-1-one. 1H-NMR (CDCl3) δ 7.22 (d, J=8.6 Hz, 1H), 7.02 (d, J=8.6 Hz, 1H), 3.90 (s, 3H), 3.32 (t, J=6.1 Hz, 2H), 3.15 (s, 3H), 2.72 (t, J=6.8 Hz, 2H), 2.06-1.99 (m, 2H); LC/MS (ESI+): 250.98 (M+H).

Workup

  1. temperaturewarmed to room temperature
  2. extractionextracted (EtOAc)
  3. washwashed with brine
  4. dry with materialthe organic layer dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customISCO purification (0 to 100% EtOAc/hexane, 40 g SiO2 column)

Sources & evidence

ORD record
ord-db697457369344bd972b90c57aa15c2c
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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