Methanesulfonic Acid → N-benzyl-7-methoxy-1,2-dihydroisoquinolin-4(3H)-one

HRID 1041593Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

To a round-bottomed flask containing methanesulfonic acid (75 mL) was added [benzyl-(3-methoxy-benzyl)-amino]-acetic acid (11.0 g, 38.5 mmol) with stirring. The mixture was heated to 100° C. for five hours whereupon LCMS showed completion of the reaction. The mixture was cooled to ambient temperature, water (300 mL) was added and the mixture was cooled in an ice-water bath and adjusted to pH 9 (10N NaOH), keeping the internal temperature below 30° C. The precipitate was collected by vacuum filtration, washed with water to neutrality, and dried to constant weight in vacuo to afford 2-benzyl-7-methoxy-2,3-dihydro-1H-isoquinolin-4-one (7.7 g, 75%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 7.83 (d, J=8 Hz, 1H), 7.34 (m, 5H), 6.95 (d, J=8 Hz, 1H), 6.90 (s, 1H), 3.82 (s, 3H), 3.76 (s, 2H), 3.71 (s, 2H), 3.27 (s, 2H); (m/e) 268 (M+1); mp 135° C. (dec.).

Workup

customcompletion of the reaction
temperatureThe mixture was cooled to ambient temperature
temperaturethe mixture was cooled in an ice-water bath
customthe internal temperature below 30° C
filtrationThe precipitate was collected by vacuum filtration
washwashed with water to neutrality
customdried to constant weight in vacuo

Sources & evidence

ORD record: ord-1a8f28919ad64806aedd1e7027514b9b
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08552186B2

Reaction notes

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