Methanol → 6-Methoxy-3-(methoxymethyl)-2-methyl-4-phenylisoquinolin-1(2H)-one

HRID 2233052Notes

Reaction equation

[CH3:1][OH:2].[H-].[Na+].Br[CH2:6][C:7]1[N:8]([CH3:26])[C:9](=[O:25])[C:10]2[C:15]([C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:14][C:13]([O:23][CH3:24])=[CH:12][CH:11]=2>CN(C)C=O>[CH3:24][O:23][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:25])[N:8]([CH3:26])[C:7]([CH2:6][O:2][CH3:1])=[C:16]2[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methanol (0.057 mL, 1.40 mmol) in 2 mL of dimethylformamide was added sodium hydride (45 mg, 60% dispersion in mineral oil, 1.11 mmol). After 10 minutes, 3-(bromomethyl)-6-methoxy-2-methyl-4-phenylisoquinolin-1(2H)-one was added (100 mg, 0.279 mmol). After 30 minutes, the reaction mixture was cooled to 0° C., and quenched with 1 mL of saturated NaHCO3 solution. The mixture was partitioned between EtOAc and saturated NaHCO3 solution, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography through SiO2 (50% EtOAc/hexane) to provide the titled product as a white solid. 1H-NMR (500 MHz, CDCl3) δ 8.43 (d, J=9.0 Hz, 1H), 7.44-7.50 (m, 3H), 7.29-7.31 (m, 2H), 6.91 (dd, J=9.0, 2.5 Hz, 1H), 6.42 (d, J=2.5 Hz, 1H), 4.18 (s, 2H), 3.75, (s, 3H), 3.69 (s, 3H), 3.24 (s, 3H) ppm. ESI+ MS: 310.23 [M+H]+.

Workup

waitAfter 30 minutes
customquenched with 1 mL of saturated NaHCO3 solution
customThe mixture was partitioned between EtOAc and saturated NaHCO3 solution
washthe organic layer was washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude residue was purified by flash chromatography through SiO2 (50% EtOAc/hexane)

Sources & evidence

ORD record: ord-71714bbd1b994b68a931cc69b02d834a
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709476B2

Reaction notes

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