Toluene → 6-Bromo-2-(1-phenyl-2-propyl)-isoquinolin-1-one

HRID 1037620Notes

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.BrC[CH:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16].[OH-].[Na+].[C:25]1(C)C=CC=CC=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.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:16]([CH3:25])[CH2:15][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[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-bromo-2-phenylpropane (160 uL, 0.8 mmol, 1.2 equiv) were combined in toluene (10 mL) and treated with 50% aq. NaOH (2 mL), and the resulting mixture was stirred rapidly and heated at 70° C. After heating for an additional 14 hours, the mixture was diluted with diethyl ether and washed with water and brine. The organic phase was dried over Na2SO4 and concentrated. Purification of the residue using flash silica gel chromatography (gradient of 2-15% ethyl acetate/hexanes) gave 6-bromo-2-(1-phenyl-2-propyl)-isoquinolin-1-one (74 mg, 0.22 mmol, 32%) as a colorless oil. This isoquinolinone (74 mg, 0.22 mmol) was converted, via Methods 1 and 2, to a 1:1 mixture of compound 6 and 6-hydroxy-2-(1-phenyl-2-propyl)-isoquinolin-1-one that was isolated as 44 mg of a white solid (33% of 6). [M−H]−=306.1 m/z. Activity: B

Workup

temperatureAfter heating for an additional 14 hours
washwashed with water and brine
dry with materialThe organic phase was dried over Na2SO4
concentrationconcentrated
customPurification of the residue

Sources & evidence

ORD record: ord-efe5a5d985cb45d18bdcd47241170492
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546564B2

Reaction notes

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