Boron trifluoride etherate → 2-[1-(3,4-dimethoxy-benzyl)-7-(1-methyl-prop-2-oxy)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-benzyl-acetamide

HRID 48850

Reaction equation

HRID 48850 reaction equation
ClC(Cl)(Cl)C(=N)O[C:5]([CH3:8])([CH3:7])C.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:42]=[CH:43][C:44]=1[O:45][CH3:46])[CH2:17][CH:18]1[C:27]2[C:22](=[CH:23][C:24]([O:29][CH3:30])=[C:25]([OH:28])[CH:26]=2)[CH2:21][CH2:20][N:19]1[CH2:31][C:32]([NH:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33].B(F)(F)F.[CH3:51]COCC.C([O-])(O)=O.[Na+]>ClCCl.C1CCCCC1.C(OCC)(=O)C.O>[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:42]=[CH:43][C:44]=1[O:45][CH3:46])[CH2:17][CH:18]1[C:27]2[C:22](=[CH:23][C:24]([O:29][CH3:30])=[C:25]([O:28][CH:5]([CH3:7])[CH2:8][CH3:51])[CH:26]=2)[CH2:21][CH2:20][N:19]1[CH2:31][C:32]([NH:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33]

Participants

9

Reactant 4

HCID 8000Boron trifluoride etherateHCID 516892Sodium BicarbonateHCID 2734700Tert-butyl 2,2,2-trichloroethanimidate2×HCID 227427542-[1-(3,4-dimethoxy-benzyl)-7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-benzyl-acetamide

Product 1

HCID 227427802-[1-(3,4-dimethoxy-benzyl)-7-(1-methyl-prop-2-oxy)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-benzyl-acetamideYield 75.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

At room temperature tert.-butyl 2,2,2-trichloroacetimidate (437 mg, 0.36 mL, 2.0 mmol) was added to a solution of 2-[1-(3,4-dimethoxy-benzyl)-7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-benzyl-acetamide (95.3 mg, 0.2 mmol) in dichloromethane (5.0 mL) and cyclohexane (5.0 mL). The reaction mixture was treated with a solution of boron trifluoride diethyl etherate (50 μL, 0.4 mmol) in 10 mL dichloromethane and stirred for 22 h. Another portion of tert.-butyl 2,2,2-trichloroacetimidate (244 mg, 0.20 mL, 1.1 mmol) was added. After stirring for three days a saturated solution of NaHCO3 (10 mL), water (10 mL) and ethyl acetate (40 mL) were added, the phases were separated and the aqueous phase was extracted three times with ethyl acetate (30 mL). The combined organic phases were concentrated in vacuo and purified by flash-chromatography to give the titled product (80.4 mg, 75%) as pale yellow oil.

Workup

  1. additionwere added
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted three times with ethyl acetate (30 mL)
  4. concentrationThe combined organic phases were concentrated in vacuo
  5. custompurified by flash-chromatography

Sources & evidence

ORD record
ord-940fa4589911448486d2b30bb65761f7
Source dataset
uspto-grants-2004_03
Patent number
US06703392B2

Linked notes

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