Water → 8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one

HRID 577483Notes

Reaction equation

[Cl:1][C:2]1[C:3]([OH:13])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.CS(O[CH:19]([CH3:24])[C:20]([F:23])([F:22])[F:21])(=O)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[C:3]([O:13][CH:19]([CH3:24])[C:20]([F:23])([F:22])[F:21])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 8-chloro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (1e, 120 mg, 0.610 mmol), 1,1,1-trifluoropropan-2-yl methanesulfonate (526 mg, 2.74 mmol), and K2CO3 (420 mg, 3.05 mmol) in dry DMF (8 mL) was stirred in a sealed-tube at 140° C. for 48 hours. To the reaction mixture was added H2O (40 mL). The mixture was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (4×30 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by preparatory TLC (EtOAc, Rf ˜0.65) to give 8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one (58a, 27 mg, 15%) as a yellow oil.

Workup

extractionThe mixture was extracted with EtOAc (2×20 mL)
washThe combined organic layers were washed with brine (4×30 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under vacuum
customThe residue was purified by preparatory TLC (EtOAc, Rf ˜0.65)

Sources & evidence

ORD record: ord-ad7e600b915a448385a0d530d6a05e23
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

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