Triphenylphosphine → 6-Isoquinolinecarboxylic acid, methyl ester

HRID 598834Notes

Reaction equation

HRID 598834 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[C:12]([O-:15])(=[O:14])C.[Na+].[C:17]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C]=O>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO>[CH:8]1[C:9]2[C:4](=[CH:3][C:2]([C:12]([O:15][CH3:17])=[O:14])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 3136816-BromoisoquinolineHCID 517045Sodium AcetateHCID 178418416HCID 178418416, compound

Product 1

HCID 152903606-Isoquinolinecarboxylic acid, methyl esterYield 267.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-bromoisoquinoline (10 g, 48 mmol), purchased from Gateway Chemical Technology, Inc., in 200 mL of 1:1 DMF:MeOH was added sodium acetate (5.0 g, 61 mmol), triphenylphosphine (3.8 g, 14 mmol), and palladium(II) acetate (2.8 g, 12 mmol). The vessel was charged with 300 kPa of carbon monoxide. The vessel was then purged. This charging purging sequence was repeated three times, then the vessel was charged with 300 kPa of CO and heated to 100° C. After 15 hours, the reaction was judged to be complete by LC/MS. The reaction was filtered through Celite (eluting with EtAOc) and the resulting mixture was concentrated under reduced pressure. The residue was taken up in 250 mL of EtOAc and washed three times with water and once with brine. The mixture was then dried over MgSO4, filtered, and concentrated under reduced pressure. Flash chromatography on silica gel (10% to 35% EtOAc/hexanes) afforded methyl isoquinoline-6-carboxylate as a white powder (7.0 g, 78% yield): LCMS (API ES) m/z 188 [M+1+].

Workup

  1. customThe vessel was then purged
  2. customThis charging purging sequence
  3. additionthe vessel was charged with 300 kPa of CO
  4. filtrationThe reaction was filtered through Celite (eluting with EtAOc)
  5. concentrationthe resulting mixture was concentrated under reduced pressure
  6. washwashed three times with water
  7. dry with materialThe mixture was then dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b695c07714f74417a83b28240137dcab
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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