Potassium Hydroxide → HCID 66706674, compound

HRID 911485Notes

Reaction equation

HRID 911485 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][C:21](=O)N(C)C)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1CCC2C(SC(=O)N(C)C)=C(Cl)C=C(Cl)C=2CC1)=O)(C)(C)C.[OH-].[K+].[Cl-].[NH4+].C1CCN2C(=NCCC2)CC1.[F:67][C:68]1[CH:75]=[CH:74][CH:73]=[CH:72][C:69]=1CBr>CO.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:69]3[CH:72]=[CH:73][CH:74]=[CH:75][C:68]=3[F:67])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 67968alpha-Bromo-o-fluorotolueneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 576562773-tert-butoxycarbonyl-7,9-dichloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66706674HCID 66706674, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine and 3-tert-butoxycarbonyl-7,9-dichloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-benzo[d]azepine (102 mg, 0.267 mmol) in methanol (2 ml), add potassium hydroxide pellets (450 mg, 8.02 mmol) and heat the mixture 3 h at 60° C. Cool to ambient temperature, add aqueous saturated ammonium chloride solution, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Dissolve the crude thiophenol thus obtained in dry DCM (2 mL) under nitrogen, and add DBU (80 □L, 0.54 mmol) and 2-fluorobenzyl bromide (65 □L, 0.54 mmol) with stirring. Stir overnight at ambient temperature, dilute with water, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(2-fluorobenzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (31 mg, 25%). Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (ES+) m/z: 322 (M+H)+.

Workup

  1. temperatureCool to ambient temperature
  2. extractionextract three times with EtOAc
  3. dry with materialdry over anhydrous Na2SO4
  4. concentrationconcentrate in vacuo
  5. dissolutionDissolve the crude thiophenol
  6. customthus obtained in dry DCM (2 mL) under nitrogen
  7. stirringStir overnight at ambient temperature
  8. extractionextract three times with EtOAc
  9. dry with materialdry over anhydrous Na2SO4
  10. concentrationconcentrate in vacuo
  11. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-f241ea6b1baf4cbbb86889c7fdf40154
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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