Sodium Iodide → 3-tert-butoxycarbonyl-7-chloro-6-[4-(1,1-dimethyl-propyl)-phenylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670545Notes

Reaction equation

HRID 1670545 reaction equation
[CH3:1][C:2]([C:6]1[CH:11]=[CH:10][C:9]([SH:12])=[CH:8][CH:7]=1)([CH3:5])[CH2:3][CH3:4].[H-].[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][C:26]2[C:29]([CH2:34]Cl)=[C:30]([Cl:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[I-].[Na+]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][C:26]2[C:29]([CH2:34][S:12][C:9]3[CH:8]=[CH:7][C:6]([C:2]([CH3:1])([CH3:5])[CH2:3][CH3:4])=[CH:11][CH:10]=3)=[C:30]([Cl:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 151982394-(1,1-Dimethylpropyl)-benzenethiolHCID 597874103-tert-Butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 673364373-tert-butoxycarbonyl-7-chloro-6-[4-(1,1-dimethyl-propyl)-phenylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 40.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
45 °C

Procedure

Dissolve 4-(1,1-dimethyl-propyl)-benzenethiol (100 mg, 0.55 mmol) in anhydrous DMF (2 mL). Add sodium hydride (32 mg, 0.78 mmol, 60% dispersion in mineral oil) at room temperature under a nitrogen atmosphere. Stir the mixture for 5 min, then add a solution of 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (214 mg, 0.55 mmol) in anhydrous DMF (2 mL). Heat the mixture to 45° C., add catalytic sodium iodide and stir the mixture at 45° C. for 6 h. Cool the reaction mixture to room temperature and quench with water. Extract the mixture with EtOAc (4×25 mL). Wash the combined organic extracts with brine. Dry the organic layer over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (20:1 to 17:3 gradient) to obtain 3-tert-butoxycarbonyl-7-chloro-6-[4-(1,1-dimethyl-propyl)-phenylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (105 mg, 40%).

Workup

  1. customat room temperature
  2. stirringstir the mixture at 45° C. for 6 h
  3. temperatureCool the reaction mixture to room temperature
  4. customquench with water
  5. extractionExtract the mixture with EtOAc (4×25 mL)
  6. washWash the combined organic extracts with brine
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (20:1 to 17:3 gradient)

Sources & evidence

ORD record
ord-2603ba0cbdd0494dadac1c5e2fd4d32f
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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