Phosphorus oxide (P4O10) → 2-cyclopentyl-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 404978Notes

Reaction equation

HRID 404978 reaction equation
[CH:1]1([N:6]([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C:7](=O)[O:8]C)[CH2:5][CH2:4][CH2:3][CH2:2]1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>O=P(Cl)(Cl)Cl>[CH:1]1([N:6]2[CH2:11][CH2:12][C:13]3[C:18](=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:7]2=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 14812Phosphorus oxide (P4O10)HCID 66799542Methyl cyclopentyl(4-methoxyphenethyl)carbamate

Product 1

HCID 667996072-cyclopentyl-7-methoxy-3,4-dihydroisoquinolin-1(2H)-oneYield 95%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

To a solution of methyl cyclopentyl(4-methoxyphenethyl)carbamate (0.830 g, 3 mmol) in POCl3 (10 mL) was added P2O5 (0.852, 6 mmol). The reaction mixture was heated at reflux for 2 h. Excess POCl3 was removed under reduced pressure and quenched with ice water. The mixture was neutralized with Na2CO3, extracted with ethyl acetate and dried over Na2SO4. Concentration of the solvent followed by chromatographic separation (silica gel, 30% EtOAc:Hexanes) afforded 2-cyclopentyl-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (0.698 g, 95%). 1HNMR (400 MHz, CDCl3): δ 7.60 (s, 1H), 7.05 (d, 1H, J=8.6 Hz), 6.93 (d, 111, J=8.6 Hz), 5.19-5.15 (m, 1H), 3.83 (s, 3H), 3.40 (t, 211, J=6.1 Hz), 2.85 (t, 2H, J=6.1 Hz), 1.90-1.89 (m, 2H), 1.72-1.53 (m, 6H). LC-MS (ESI) Calcd for C15H19NO2 [M+H]+: 246.14. Found: 246.00.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. customExcess POCl3 was removed under reduced pressure
  4. customquenched with ice water
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over Na2SO4
  7. customConcentration of the solvent followed by chromatographic separation (silica gel, 30% EtOAc:Hexanes)

Sources & evidence

ORD record
ord-9d461b1f02f54406bcaa6a72292e2d89
Source dataset
uspto-grants-2014_06
Patent number
US08748632B2

Reaction notes

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