Potassium Hydroxide → HCID 66706900, compound

HRID 911731Notes

Reaction equation

HRID 911731 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20]C(=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].[OH-].[K+].[Cl-].[NH4+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([SH:20])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66706900HCID 66706900, compoundYield 1,000%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Dissolve 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (200 mg, 0.52 mmol) in methanol (12 mL) and add potassium hydroxide (0.935 g, 16.66 mmol). Heat at 60° C. for 4 h Cool the reaction mixture to ambient temperature, add aqueous saturated ammonium chloride and concentrate in vacuo. Partition the residue between EtOAc and water. Dry the organic phase over anhydrous Na2SO4 and concentrate in vacuo to give 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.16 g, 5.2 mmol). Dissolve the crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.16 g, 0.52 mmol) in anhydrous DMSO (5 mL) and add triethylamine (0.435 mL, 3.12 mmol) and 4-(3-cyano-benzoyl)benzyl bromide (289 mg, 0.96 mmol). Heat the solution at 40° C. overnight. Cool to ambient temperature, dilute the mixture with hexane/EtOAc (1:1, 100 mL), and wash the organic solution sequentially with brine and ice-cold water. Dry the organic layer over anhydrous Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (9:1, 4:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[4-(3-cyanobenzoyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as oil (212 mg, 77%).

Workup

  1. temperatureCool the reaction mixture to ambient temperature
  2. concentrationconcentrate in vacuo
  3. customPartition the residue between EtOAc and water
  4. dry with materialDry the organic phase over anhydrous Na2SO4
  5. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-3f4b956cb766492d9705dea9c4f3cf46
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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