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

HRID 2403052Notes

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-adba045285dd49b1ba45e307749c1f2a
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802064B2

Reaction notes

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