Dichloromethane → 7-Isoquinolinecarboxylic acid, 1-methoxy-, methyl ester

HRID 711062Notes

Reaction equation

HRID 711062 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][CH3:13])=[CH:4][CH:3]=1.[C:14]([O-:17])(=[O:16])C.[Na+].Cl[CH2:20]Cl>CO.Cl[Pd]Cl.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]>[CH3:13][O:12][C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([C:14]([O:17][CH3:20])=[O:16])[CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 517045Sodium AcetateHCID 674916117-Bromo-1-methoxyisoquinoline

Product 1

HCID 674914067-Isoquinolinecarboxylic acid, 1-methoxy-, methyl esterYield 647.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 7-bromo-1-methoxyisoquinoline (520 mg, 2.2 mmol) in methanol (30 mL) was added sodium acetate (517 mg, 6.30 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (257 mg, 0.315 mmol). The mixture was evacuated and backfilled with nitrogen three times. The reaction vessel was then pressurized to 25 psi carbon monoxide. The reaction was heated to 70° C. and was agitated for 20 hours. The reaction was filtered, rinsing with methanol. The filtrate was concentrated. The resulting residue was taken up in dichloromethane and the remaining solids were filtered off. The filtrate was concentrated and purified by flash column chromatography (0-100% ethyl acetate/heptanes) to give the title compound (443 mg, 93%) as a white solid. +ESI (M+H) 218.1; 1H NMR (400 MHz, DMSO-d6, δ): 8.77 (d, J=0.8 Hz, 1H), 8.20 (dd, J=8.6, 1.8 Hz, 1H), 8.13 (d, J=5.9 Hz, 1H), 8.00 (d, J=8.6 Hz, 1H), 7.46 (d, J=5.9 Hz, 1H), 4.08 (s, 3H), 3.90 (s, 3H).

Workup

  1. customThe mixture was evacuated
  2. filtrationThe reaction was filtered
  3. washrinsing with methanol
  4. concentrationThe filtrate was concentrated
  5. filtrationthe remaining solids were filtered off
  6. concentrationThe filtrate was concentrated
  7. custompurified by flash column chromatography (0-100% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-fa907c3d4c8845ba8b1b27bb6882aae8
Source dataset
uspto-grants-2015_11
Patent number
US09181252B2

Reaction notes

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