(1-Bromoethyl)benzene → 6-Bromo-2-(1-phenylethyl)-isoquinolin-1-one

HRID 1037618Notes

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.Br[CH:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C(OCC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[CH:6]=[CH:5]2

Participants

Conditions

Temperature: 70 °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 1-bromoethylbenzene (160 uL, 0.8 mmol, 1.2 equiv) were combined in toluene (7 mL) and treated with 50% aq. NaOH (2 mL) and the resulting mixture was stirred rapidly while heating to 70° C. After additional stirring for 14 hours, the mixture was diluted with diethyl ether and washed with water and brine. The organic phase was dried over Na2SO4. Addition of silica gel, concentration, and purification of the residue using flash silica gel chromatography (gradient 2→12% ethyl acetate/hexanes) gave 6-bromo-2-(1-phenylethyl)-isoquinolin-1-one (227 mg, 0.67 mmol, quant.) as a yellowish oil. This isoquinolinone (220 mg, 0.67 mmol) was converted, via Methods 1 and 2, to compound 4 (109 mg, 56%) and isolated as a white solid. [M−H]−=292.1 m/z. Activity: B

Workup

stirringAfter additional stirring for 14 hours
washwashed with water and brine
dry with materialThe organic phase was dried over Na2SO4
additionAddition of silica gel, concentration, and purification of the residue

Sources & evidence

ORD record: ord-8fdd81ce166f4d3282a00cec1caa2c74
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546564B2

Reaction notes

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