Sodium Chloride → 7-Ethyl-8-trifluoromethyl-1,2,3,4-tetrahydro-benzo[b]azepin-5-one

HRID 507053Notes

Reaction equation

HRID 507053 reaction equation
COC([CH:5]1[CH2:11][CH2:10][N:9](C(OC(C)C)=O)[C:8]2[CH:18]=[C:19]([C:24]([F:27])([F:26])[F:25])[C:20]([CH2:22][CH3:23])=[CH:21][C:7]=2[C:6]1=[O:28])=O.[Cl-].[Na+]>CS(C)=O.O.C(OCC)(=O)C>[CH2:22]([C:20]1[C:19]([C:24]([F:27])([F:25])[F:26])=[CH:18][C:8]2[NH:9][CH2:10][CH2:11][CH2:5][C:6](=[O:28])[C:7]=2[CH:21]=1)[CH3:23]

Participants

6

Reactant 2

HCID 5234Sodium ChlorideHCID 594324487-Ethyl-5-oxo-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester

Product 1

HCID 594325027-Ethyl-8-trifluoromethyl-1,2,3,4-tetrahydro-benzo[b]azepin-5-oneYield 61%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Heat a mixture of 7-ethyl-5-oxo-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1,4-dicarboxylic acid 1-isopropyl ester 4-methyl ester (23.55 g, 58.61 mmol), sodium chloride (52.50 g), and water (10.0 mL) in dimethylsulfoxide (500 mL) at reflux for 46 h. Allow the mixture to cool to room temperature and dilute it with water (200 mL) and ethyl acetate (200 mL). Wash the organic layer with water (350 mL). Dry the organic layer over anhydrous sodium sulfate and filter. Remove the solvents under reduced pressure and purify the resulting residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0 to 15%), to provide the title compound as a yellow solid (9.17 g, 61%) TLC Rf 0.32 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.10-1.23 (m, 3H), 2.13-2.21 (m, 2H), 2.63-2.71 (m, 2H), 2.83-2.92 (m, 2H), 3.22-3.31 (m, 2H), 4.74 (bs, 1H), 7.03 (s, 1H), 7.68 (s, 1H).

Workup

  1. temperatureHeat
  2. temperatureat reflux for 46 h
  3. washWash the organic layer with water (350 mL)
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter
  6. customRemove the solvents under reduced pressure
  7. custompurify the resulting residue by column chromatography on silica gel
  8. washeluting with ethyl acetate/hexanes (0 to 15%)

Sources & evidence

ORD record
ord-62993b0eeb0a49ad98a874ad340cb94c
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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