Potassium Hydroxide → HCID 66706946, compound

HRID 911419Notes

Reaction equation

HRID 911419 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+].[H-].[Na+].C1(C)C=CC(S(O[CH2:40][C@H:41]2[O:45][C:44](=[O:46])[CH2:43][CH2:42]2)(=O)=O)=CC=1>CO.CCOC(C)=O.[NH4+].[Cl-]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:40][C@@H:41]3[CH2:42][CH2:43][C:44](=[O:46])[O:45]3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 2724793(S)-(5-Oxotetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonateHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66706946HCID 66706946, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-benzo[d]azepine (137 mg, 0.356 mmol) in methanol (2 mL) add potassium hydroxide pellets (640 mg, 11.4 mmol) and heat for 3 h at 50° C. Cool to ambient temperature, add saturated aqueous NH4Cl, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Dissolve the crude thiophenol thus obtained in dry DMF (2 mL), and add with stirring sodium hydride (18 mg, 0.713 mmol, 95% dispersion), followed by (S)-(+)-dihydro-5-(p-tolylsulfonyloxymethyl)-2-(3H)-furanone (144 mg, 0.533 mmol). Continue stirring overnight at ambient temperature, then dilute cautiously with EtOAc and cold saturated aqueous NH4Cl. Extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (7:3) to give the title compound as a colorless oil.

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 DMF (2 mL)
  7. extractionExtract three times with EtOAc
  8. dry with materialdry over anhydrous Na2SO4
  9. concentrationconcentrate in vacuo
  10. customPurify by chromatography on silica gel eluting with hexane/EtOAc (7:3)

Sources & evidence

ORD record
ord-cc2aea9bef794d20aaa02b46bb1d7771
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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