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

HRID 1040643Notes

Reaction equation

HRID 1040643 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) δδ 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-f61d01fd412245b58d399527de973c48
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…