Carbamate → 3-tert-butoxycarbonyl-6-(4-carboxybenzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911462Notes

Reaction equation

HRID 911462 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].[OH-].[K+].BrC[C:30]1[CH:39]=[CH:38][C:33]([C:34]([O:36]C)=[O:35])=[CH:32][CH:31]=1.C(=O)([O-])N.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.C([O-])(O)=O.[Na+]>CO.[NH4+].[Cl-]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:30]3[CH:39]=[CH:38][C:33]([C:34]([OH:36])=[O:35])=[CH:32][CH:31]=3)=[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 276CarbamateHCID 14797Potassium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 256687Methyl 4-(bromomethyl)benzoateHCID 516892Sodium BicarbonateHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 576565513-tert-butoxycarbonyl-6-(4-carboxybenzylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
57.5 °C

Procedure

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.0 g, 2.6 mmol) in methanol (15 mL) under nitrogen, add with stirring potassium hydroxide (4.5 g, 80.3 mmol) at ambient temperature. Heat at 55-60° C. for 2 h, cool to ambient temperature, and add methyl 4-bromomethylbenzoate (1.2 g, 5.2 mmol). TLC after 20 min shows formation of product; however, after 4 h at ambient temperature both TLC and LC/MS indicate complete hydrolysis of the ester and the carbamate. Dilute with saturated aqueous NH4Cl, extract three times with EtOAc, dry over anhydrous MgSO4, and concentrate in vacuo. Dissolve the crude material in THF (10 mL), treat with di-tert-butyl-dicarbonate (2 equiv) and saturated aqueous NaHCO3 (10 mL), and stir overnight. Extract three times with EtOAc, dry over anhydrous MgSO4 and concentrate in vacuo to give the desired intermediate as an oil that was used without purification [2.32 g, 50% purity with (Boc)2O]. MS (ES+) m/z 348 (M+H−Boc)+.

Workup

  1. temperaturecool to ambient temperature
  2. waithowever, after 4 h at ambient temperature both TLC and LC/MS indicate complete
  3. extractionextract three times with EtOAc
  4. dry with materialdry over anhydrous MgSO4
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the crude material in THF (10 mL)
  7. extractionExtract three times with EtOAc
  8. dry with materialdry over anhydrous MgSO4
  9. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-dd73da65f5c24eb5966660c00bc8de24
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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