Phosphorus oxide (P4O10) → 5-Chloro-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 525845Notes

Reaction equation

HRID 525845 reaction equation
[Cl:1][C:2]1[C:15]([O:16][CH3:17])=[C:14]([O:18][CH3:19])[CH:13]=[CH:12][C:3]=1[CH2:4][CH2:5][NH:6][C:7](=O)[O:8]CC.C[Si](C)(C)O[Si](C)(C)C.P(Cl)(Cl)(Cl)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>ClCCl>[Cl:1][C:2]1[C:15]([O:16][CH3:17])=[C:14]([O:18][CH3:19])[CH:13]=[C:12]2[C:3]=1[CH2:4][CH2:5][NH:6][C:7]2=[O:8]

Participants

6

Reactant 4

HCID 14812Phosphorus oxide (P4O10)HCID 24764HexamethyldisiloxaneHCID 24813Phosphorus oxychlorideHCID 86732714Ethyl 2-chloro-3,4-dimethoxyphenethylcarbamate

Product 1

HCID 642812755-Chloro-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-oneYield 20.24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To ethyl 2-chloro-3,4-dimethoxyphenethylcarbamate 3 (2 g, 6.95 mmol) in 1,1,1,3,3,3-hexamethyldisiloxane (7.39 ml, 34.8 mmol) in a 20 ml microwave tube was added phosphorous oxichloride (6.48 ml, 69.5 mmol) and phosphorus pentoxide (4.93 g, 34.8 mmol). Microwaved at 150° C. (high absorption setting) for 1 hour. Solvent removed and poured on to the ice. Neutralized with 2M sodium hydroxide and extracted with dichloromethane. Dried over magnesium sulfate and chromotagraphed eluting with 0-20% methanol:dichloromethane to give 5-chloro-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-one (340 mg, 1.407 mmol, 20.24% yield).) LCMS (M+H)+: 242.1

Workup

  1. customMicrowaved at 150° C. (high absorption setting) for 1 hour
  2. customSolvent removed
  3. additionpoured on to the ice
  4. extractionextracted with dichloromethane
  5. dry with materialDried over magnesium sulfate
  6. washchromotagraphed eluting with 0-20% methanol

Sources & evidence

ORD record
ord-a52eb9ff55904a758770a83da9ad9327
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

Loading…