Phosphorus oxychloride → 6-Methoxy-1-[4-(phenylmethoxy)benzyl]-1,2,3,4-tetrahydroisoquinoline

HRID 1180146

Reaction equation

HRID 1180146 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][NH:11][C:12](=O)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=2)[CH:6]=[CH:7][CH:8]=1.P(Cl)(Cl)(Cl)=O.[BH4-].[Na+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:6](=[CH:7][CH:8]=1)[CH:12]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16][CH:15]=1)[NH:11][CH2:10][CH2:9]2

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 4311764Sodium borohydrideHCID 12950733N-[2-(3-methoxyphenyl)ethyl]-2-[4-(phenylmethoxy)phenyl]acetamide

Product 1

HCID 129507356-Methoxy-1-[4-(phenylmethoxy)benzyl]-1,2,3,4-tetrahydroisoquinolineYield 28%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of N-[2-(3-methoxyphenyl)ethyl]-2-[4-(phenylmethoxy)phenyl]acetamide (5.739 g, 15.3 mmol) and phosphorous oxychloride (15 mL) in acetonitrile (40 mL) under nitrogen was heated at 80° C. for 5 hours. Solvents were evaporated. Ethyl acetate was added and evaporated three times. The residue was dissolved in methanol (50 mL) and sodium borohydride (2.00 g, 52.9 mmol) was carefully added to the solution in small portions. After 2 hours, the reaction was quenched with water and extracted with CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated. The residue was then purified by chromatography (SiO2, 0-10% methanol/CH2Cl2) to provide the title compound (1.54 g, 28% yield): 1H NMR (CDCl3) 7.36 (m, 6H), 7.12 (d, 2H), 6.91 (d, 2H), 6.73 (dd, 1H), 6.62 (m, 1H), 5.04 (s, 2H), 4.97 (t, 1H), 4.17 (br, 1H), 3.78 (s, 3H), 3.73 (m, 1H), 3.16 (m, 2H), 2.83 (m, 3H); ES-MS (m/z) 360 [M+H]+.

Workup

  1. customSolvents were evaporated
  2. additionEthyl acetate was added
  3. customevaporated three times
  4. dissolutionThe residue was dissolved in methanol (50 mL)
  5. customthe reaction was quenched with water
  6. extractionextracted with CH2Cl2
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was then purified by chromatography (SiO2, 0-10% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-7ac76c8816574993b91e8eb61ddfa85d
Source dataset
uspto-grants-2007_10
Patent number
US07279489B2

Linked notes

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