Boron tribromide → 2-[3-(3-chlorophenyl)-7-hydroxy-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide

HRID 602280Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:21][C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])[C:10](=[O:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([O:18]C)[CH:12]=3)[CH:5]=[CH:6][CH:7]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH2:21][C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[O:23])[C:10](=[O:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([OH:18])[CH:12]=3)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2-[3-(3-chlorophenyl)-7-methoxy-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (886 mg, 2.30 mmol) in dry DCM (25 mL) was cooled to −78° C. and a solution of BBr3 (1 M in DCM, 20.3 mL, 20.3 mmol) was added dropwise. After 1 h, the cooling bath was removed and the mixture was allowed to stir an additional 17.5 h, then cooled to 0° C. and quenched by dropwise addition of sat. NaHCO3 (aq.) (15 mL). The aqueous mixture was extracted with IPA:DCM (1:3, v/v) (4×25 mL). The combined organic extracts were washed with brine (25 mL), dried (MgSO4) and concentrated to give the crude product, which was recrystallized from EtOH to give pure 2-[3-(3-chlorophenyl)-7-hydroxy-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (INTERMEDIATE III.7) (530 mg, 1.43 mmol, 62%) as white solid.

Workup

customthe cooling bath was removed
customquenched by dropwise addition of sat. NaHCO3 (aq.) (15 mL)
extractionThe aqueous mixture was extracted with IPA:DCM (1:3
washThe combined organic extracts were washed with brine (25 mL)
dry with materialdried (MgSO4)
concentrationconcentrated
customto give the crude product, which
customwas recrystallized from EtOH

Sources & evidence

ORD record: ord-acd1c3bd998d4316bf42cc3b9631ff24
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07906504B2

Reaction notes

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