Sodium Iodide → Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

HRID 516985Notes

Reaction equation

HRID 516985 reaction equation
CO[C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:6][C:5]=1[CH2:17]Cl.[CH3:20][O:21][C:22](=[O:35])[CH2:23][NH:24]S(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].C[O-].[Na+]>CN(C=O)C.CO.O.C(O)(=O)C>[CH3:20][O:21][C:22]([C:23]1[N:24]=[CH:17][C:5]2[C:4]([C:3]=1[OH:19])=[CH:9][CH:8]=[C:7]([O:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH:6]=2)=[O:35]

Participants

10

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 562880Methyl 2-(4-methylphenylsulfonamido)acetateHCID 10942334Sodium MethoxideHCID 86709143Methyl 2-(chloromethyl)-4-phenoxybenzoate

Product 1

HCID 86709142Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A reactor was charged with a solution of 2-chloromethyl-4-phenoxybenzoic acid methyl ester (˜68 Kg) in DMF, and stirring was initiated. The reactor was then charged with p-toluenesulfonylglycine methyl ester (66 Kg), potassium carbonate (60 Kg), and sodium iodide (4 Kg). The mixture was heated to at least 50° C. until reaction completion. The mixture was cooled. Sodium methoxide in methanol was charged and the mixture was stirred until reaction completion. Acetic acid and water were added, and the mixture was stirred, filtered and washed with water. Solid was purified by acetone trituration and dried in an oven giving 1a (Yield from step b): 58%; HPLC: 99.4%). 1H NMR (200 MHz, DMSO-d6) δ 11.60 (s, 1H), 8.74 (s, 1H), 8.32 (d, J=9.0 Hz, 1H), 7.60 (dd, J=2.3 & 9.0 Hz, 1H), 7.49 (m, 3H), 7.24 (m, 3H), 3.96 (s, 3H); MS-(+)-ion M+1=296.09

Workup

  1. temperatureThe mixture was heated to at least 50° C. until reaction completion
  2. temperatureThe mixture was cooled
  3. stirringthe mixture was stirred until reaction completion
  4. stirringthe mixture was stirred
  5. filtrationfiltered
  6. washwashed with water
  7. customSolid was purified by acetone trituration
  8. customdried in an oven

Sources & evidence

ORD record
ord-934a1ba4c8fb4dcebb7ec194e985bf71
Source dataset
uspto-grants-2015_08
Patent number
US09115085B2

Reaction notes

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