1,2-Dichloroethane → HCID 66707056, compound

HRID 911548Notes

Reaction equation

HRID 911548 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][CH2:22][CH2:23][C:24]([O:26]C)=O)=[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-].[Li+].[Cl-].[NH4+].C(Cl)CCl.ON1C2C=CC=CC=2N=N1.[CH2:46]([N:48](CC)[CH2:49]C)C.CNC>O1CCOCC1.O.[Cl-].[Na+].O.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][CH2:22][CH2:23][C:24](=[O:26])[N:48]([CH3:49])[CH3:46])=[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

11

Reactant 7

HCID 111,2-DichloroethaneHCID 674DimethylamineHCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 66707037HCID 66707037, compound

Product 1

HCID 66707056HCID 66707056, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)SolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Treat a solution of 3-tert-butoxycarbonyl-7-chloro-6-(3-methoxycarbonyl-propylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (385 mg, 0.90 mmol) in dioxane/water (1:1, 3.5 mL) with lithium hydroxide (43.0 mg, 1.01 mmol) at 80° C. for 1.5 h. Cool to ambient temperature, add aqueous saturated ammonium chloride and brine, extract three times with ethyl ether, dry over anhydrous MgSO4, and concentrate in vacuo. Dissolve the residue in DCM (3.5 mL) and add EDC (162 mg, 0.84 mmol), 1-hydroxybenzotriazole (91.0 mg, 0.67 mmol), triethylamine (0.20 mL, 1.35 mmol), and dimethylamine (0.700 mL, 1.35 mmol). Stir overnight at ambient temperature. Dilute with water, extract with ethyl ether, dry over anhydrous MgSO4; and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc/methanol 60:40:1 to give 3-tert-butoxycarbonyl-7-chloro-6-(3-dimethylcarbamoyl-propylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine.

Workup

  1. extractionextract three times with ethyl ether
  2. dry with materialdry over anhydrous MgSO4
  3. concentrationconcentrate in vacuo
  4. dissolutionDissolve the residue in DCM (3.5 mL)
  5. extractionextract with ethyl ether
  6. dry with materialdry over anhydrous MgSO4
  7. concentrationand concentrate in vacuo
  8. customPurify by chromatography on silica gel eluting with hexane/EtOAc/methanol 60:40:1

Sources & evidence

ORD record
ord-73044f096a0446b6bf75b1437696301a
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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