Water → 2,9-dichloro-7-(2,6-difluorophenyl)-5H-pyrido[3,4-d][2]-benzazepine

HRID 2237399Notes

Reaction equation

HRID 2237399 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[CH:10]=[N:11][C:12]([Cl:32])=[CH:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[C:22](=O)[C:23]1[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=1[F:30])(C)(C)C.FC(F)(F)C(O)=O.O.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[Cl:32][C:12]1[N:11]=[CH:10][C:9]2[CH2:8][N:7]=[C:22]([C:23]3[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=3[F:30])[C:16]3[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:15]=3[C:14]=2[CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 59302624Tert-butyl({6-chloro-4-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]pyridin-3-yl}-methyl)carbamate

Product 1

HCID 593026122,9-dichloro-7-(2,6-difluorophenyl)-5H-pyrido[3,4-d][2]-benzazepineYield 86.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Tert-butyl({6-chloro-4-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]pyridin-3-yl}-methyl)carbamate (165.0 mg, 0.3345 mmol) was dissolved in methylene chloride (5 mL). Trifluoroacetic acid (5 mL, 0.06 mol) was added and the reaction was stirred at room temperature under an atmosphere of nitrogen overnight. Water (20 mL) and methylene chloride (15 mL) were added and the resulting mixture was stirred while solid sodium carbonate (4.50 g, 0.04 mol) was slowly added with stirring. The resulting basic mixture was stirred at room temperature for 30 minutes and then transferred to a separatory funnel. The organic layer was separated and the aqueous phase was extracted with additional methylene chloride (10 mL). The organic extracts were combined, washed with water (10 mL) and brine (10 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting white solid was purified by column chromatography on silica gel (elution gradient from dichloromethane to 7.5% ethyl acetate/dichloromethane) to yield 2,9-dichloro-7-(2,6-difluorophenyl)-5H-pyrido[3,4-d][2]-benzazepine (108 mg, 86%) as a white solid. The product structure was confirmed by NMR and MS.

Workup

  1. additionwas slowly added
  2. stirringwith stirring
  3. stirringThe resulting basic mixture was stirred at room temperature for 30 minutes
  4. customtransferred to a separatory funnel
  5. customThe organic layer was separated
  6. extractionthe aqueous phase was extracted with additional methylene chloride (10 mL)
  7. washwashed with water (10 mL) and brine (10 mL)
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting white solid was purified by column chromatography on silica gel (elution gradient from dichloromethane to 7.5% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-da9a8a8ecd13409892bb3d4a75407a93
Source dataset
uspto-grants-2010_05
Patent number
US07718648B2

Reaction notes

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