Hydrochloric Acid → 3-({1-[1-(4-Chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)-N-propylpropane-1-sulfonamide hydrochloride

HRID 242090Notes

Reaction equation

HRID 242090 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH2:23][CH2:24][CH2:25][S:26]([NH:29][CH2:30][CH2:31][CH3:32])(=[O:28])=[O:27])[CH:20]=4)[CH2:15][CH2:14][N:13]=3)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[BH4-].[Na+].Cl>CO.O.C(O)(C)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH2:23][CH2:24][CH2:25][S:26]([NH:29][CH2:30][CH2:31][CH3:32])(=[O:27])=[O:28])[CH:20]=4)[CH2:15][CH2:14][NH:13]3)[CH2:9][CH2:10][CH2:11]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 582462893-({1-[1-(4-Chlorophenyl)cyclobutyl]-3,4-dihydroisoquinolin-7-yl}oxy)-N-propylpropane-1-sulfonamide

Product 1

HCID 668686893-({1-[1-(4-Chlorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)-N-propylpropane-1-sulfonamide hydrochloride

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

3-({1-[1-(4-Chlorophenyl)cyclobutyl]-3,4-dihydroisoquinolin-7-yl}oxy)-N-propylpropane-1-sulfonamide (260 mg, 0.547 mmol) was dissolved in methanol (5 mL) and water (0.2 mL). Sodiumborohydride (41.4 mg, 1.095 mmol) was added in small portions at room temperature and the reaction mixture was stirred over night. 5N Hydrochloric acid in isopropanol was added until the reaction mixture became acidic. Stirring was continued for 30 min at room temperature. The reaction mixture was concentrated in vacuo. The crude product was dissolved in dichloromethane. Aqueous saturated NaHCO3 solution (10 mL) and water (10 mL) were added and the aqueous layer was extracted with dichloromethane (2×). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography (silica, first dichloromethane, then dichloromethane:methanol=80:1). The purified product was treated with 2N hydrochloric acid in diethylether. The diethylether was removed by destillation. Yield: 120 mg (0.234 mmol, 42.7%, colorless foam).

Workup

  1. stirringStirring
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe crude product was dissolved in dichloromethane
  4. additionAqueous saturated NaHCO3 solution (10 mL) and water (10 mL) were added
  5. extractionthe aqueous layer was extracted with dichloromethane (2×)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (silica, first dichloromethane
  9. additionThe purified product was treated with 2N hydrochloric acid in diethylether
  10. customThe diethylether was removed by destillation

Sources & evidence

ORD record
ord-a8b4f7d0039d4d9abae3539b7520ab86
Source dataset
uspto-grants-2014_02
Patent number
US08653100B2

Reaction notes

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