Tributylphosphine → 2-(4-Fluorophenyl)-1-[4-(1-methylpyrrolidin-3-yloxy)benzyl]-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline

HRID 1180179Notes

Reaction equation

HRID 1180179 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:14]=3)[CH:9]2[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)=[CH:4][CH:3]=1.[CH3:34][N:35]1[CH2:39][CH2:38][CH:37](O)[CH2:36]1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1.C(=O)(O)[O-].[Na+].C(Cl)Cl.CO.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:14]=3)[CH:9]2[CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH:37]3[CH2:38][CH2:39][N:35]([CH3:34])[CH2:36]3)=[CH:31][CH:32]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 930741-Methyl-3-pyrrolidinolHCID 234407672-(4-Fluorophenyl)-1-(4-hydroxybenzyl)-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 234408322-(4-Fluorophenyl)-1-[4-(1-methylpyrrolidin-3-yloxy)benzyl]-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinolineYield 56.3%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 2-(4-fluorophenyl)-1-(4-hydroxybenzyl)-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline (0.450 g, 1.02 mmol) in THF (5 ml) was added 1-methyl-3-pyrrolidinol (0.22 ml, 2.04 mmol), tri-n-butyl-phosphine (0.5 ml, 2.04 mmol) and 1,1′ azodicarbonyl dipiperidine (0.5 g, 2.04 mmol) respectively. Dichloromethane (4 ml) was added and the reaction was allowed to stir overnight. The reaction was diluted with aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried with MgSO4, filtered and concentrated. The product was purified by radial chromatography (100% CH2Cl2, then CH2Cl2/MeOH, 95:5) to yield the title compound (0.30 g, 56% yield): ES-MS (m/z) 523 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by radial chromatography (100% CH2Cl2

Sources & evidence

ORD record
ord-b50b8e84c4ab43c384a3148dd620ba61
Source dataset
uspto-grants-2007_10
Patent number
US07279489B2

Reaction notes

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