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

HRID 2119489Notes

Reaction equation

HRID 2119489 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-3700b7bd1a2c4270ae3c0b957a029a4f
Source dataset
uspto-grants-2004_02
Patent number
US06686351B2

Reaction notes

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