Benzyl Bromide → 2-Benzyl-6-bromo-isoquinolin-1-one

HRID 1037616Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[N:7][CH:6]=[CH:5]2.[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.CC(OC)(C)C>[CH2:13]([N:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=2)[C:8]1=[O:12])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 90 °C

Procedure

6-Bromo-1-hydroxyisoquinoline (150 mg, 0.67 mmol, 1.0 equiv), tetrabutylammonium bromide (25 mg, 0.07 mmol, 0.1 equiv), and benzyl bromide (95 uL, 0.8 mmol, 1.2 equiv) were combined in toluene (7 mL), and treated with 50% aq. NaOH (2 mL) after which point the resulting mixture was stirred rapidly at 90° C. After 80 min, the mixture was diluted with MTBE and washed with water and brine. The organic phase was dried over Na2SO4. Addition of silica gel, concentration, and purification of the residue by flash silica gel chromatography (gradient of 2-12% ethyl acetate/hexanes) provided 2-benzyl-6-bromo-isoquinolin-1-one (221 mg, 0.67 mmol, quantitative) which was then converted, via Methods 1 and 2, to compound 2 (91 mg, 49%) and isolated as a light-brown solid. [M−H]−=278.1 m/z. Activity: B

Workup

washwashed with water and brine
dry with materialThe organic phase was dried over Na2SO4
additionAddition of silica gel, concentration, and purification of the residue by flash silica gel chromatography (gradient of 2-12% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-15d7b2508c94461a8d1fa24192750fcd
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546564B2

Reaction notes

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