Trifluoroacetic anhydride → 2,2,2-Trifluoro-1-(7-methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanone

HRID 1687047Notes

Reaction equation

HRID 1687047 reaction equation
[CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1.[F:14][C:15]([F:26])([F:25])[C:16](O[C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])=[O:17].[N+:27]([O-:30])([O-:29])=[O:28].[K+]>C(#N)C>[F:14][C:15]([F:26])([F:25])[C:16]([N:9]1[CH2:10][CH2:11][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:13]([N+:27]([O-:29])=[O:28])=[CH:12][C:6]=2[CH2:7][CH2:8]1)=[O:17].[F:23][C:20]([F:21])([F:22])[C:19]([N:9]1[CH2:10][CH2:11][C:5]2[C:4]([N+:27]([O-:30])=[O:28])=[C:3]([O:2][CH3:1])[CH:13]=[CH:12][C:6]=2[CH2:7][CH2:8]1)=[O:24]

Participants

6

Reactant 3

HCID 9845Trifluoroacetic anhydrideHCID 24434Potassium NitrateHCID 138533487-Methoxy-2,3,4,5-tetrahydro-1h-3-benzazepine

Product 2

HCID 866338662,2,2-Trifluoro-1-(7-methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanoneYield 38%HCID 866338672,2,2-Trifluoro-1-(7-methoxy-6-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanoneYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Into a 1-neck round-bottom flask 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (17.00 g, 0.096 mol) was dissolved in acetonitrile (100 mL). Trifluoroacetic anhydride (47.4 mL, 0.34 mol) was added at −20° C. After 10 minutes potassium nitrate (9.7 g, 0.096 mol) was added at the same temperature, and the reaction mixture was stirred for 1.5 hours. The reaction was quenched by addition of diluted NaHCO3, and allowed to warm to room temperature. Partition between saturated aqueous Na2CO3 and dichloromethane, extraction, drying (MgSO4), filtration, and concentration, provided the crude product. Flash chromatography separation on SiO2 with dichloromethane (100%) provided 2,2,2-trifluoro-1-(7-methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanone (11.5 g, 38%) and 2,2,2-trifluoro-1-(7-methoxy-6-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanone (7.5 g, 25%). 2,2,2-Trifluoro-1-(7-methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanone: 1H-NMR (CDCl3; amide rotamers observed) δ 7.72(1H), 6.89 (1H), 3.95 (3H), 3.65-3.85 (4H), 2.95-3.07 (4H); LC/MS (ESI+): 319.20 (M+H). 2,2,2-Trifluoro-1-(7-methoxy-6-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanone: 1H-NMR (CDCl3; amide rotamers observed) δ 7.24 (1H), 6.85 (1H), 3.88 (s, 3H), 3.65-3.81 (4H), 2.80-3.05 (4H).

Workup

  1. customThe reaction was quenched by addition of diluted NaHCO3
  2. customPartition between saturated aqueous Na2CO3 and dichloromethane, extraction
  3. customdrying
  4. filtration(MgSO4), filtration, and concentration
  5. customprovided the crude product
  6. customFlash chromatography separation on SiO2 with dichloromethane (100%)

Sources & evidence

ORD record
ord-8fbbc22c34644c31b90288d40903af04
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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