Methanol → HCID 178497287, compound

HRID 533425Notes

Reaction equation

HRID 533425 reaction equation
Cl.Br[C:3]1[CH:12]=[C:11]2[C:6]([C:7]([F:14])=[CH:8][N:9]=[C:10]2[OH:13])=[CH:5][CH:4]=1.C(N(CC)CC)C.CN1[C:27](=[O:28])CCC1.[C]=O.[CH3:31][OH:32]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:14][C:7]1[C:6]2[C:11](=[CH:12][C:3]([C:31]([O:28][CH3:27])=[O:32])=[CH:4][CH:5]=2)[C:10]([OH:13])=[N:9][CH:8]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidoneHCID 178418416HCID 178418416, compoundHCID 178479649HCID 178479649, compound

Product 1

HCID 178497287HCID 178497287, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
80 °C

Procedure

A mixed liquid of 7-bromo-4-fluoroisoquinolin-1-ol hydrochloride (3.0 g), palladium (II) acetate (484 mg), 1,1′-bis(diphenylphosphino)ferrocene (1.2 g), triethylamine (4.4 g), NMP (60 mL), and methanol (60 mL) was stirred at room temperature for 15 minutes while carbon monoxide gas was passed therethrough. The reaction was further heated under stirring in an oil bath at 80° C. for 16 hours under a carbon monoxide gas atmosphere at 1 atm. The reaction mixture was returned to room temperature, the insoluble materials were separated by filtration, and then the precipitate was concentrated under reduced pressure. The resulting residue was diluted with water, and then the precipitate was collected by filtration to obtain methyl 4-fluoro-1-hydroxyisoquinoline-7-carboxylate (2.3 g).

Workup

  1. temperatureThe reaction was further heated
  2. customwas returned to room temperature
  3. customthe insoluble materials were separated by filtration
  4. concentrationthe precipitate was concentrated under reduced pressure
  5. additionThe resulting residue was diluted with water
  6. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-9849db07da1f4c918176d22222fc9e05
Source dataset
uspto-grants-2014_10
Patent number
US08853242B2

Reaction notes

Loading…