Ammonium Chloride → (rac)-4-Bromo-8-(3,4-dimethylphenyl)-5,6,7,8-tetrahydroisoquinolin-8-ol

HRID 714043

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([CH3:9])[CH:3]=1.[Li]CCCC.[Br:15][C:16]1[C:25]2[CH2:24][CH2:23][CH2:22][C:21](=[O:26])[C:20]=2[CH:19]=[N:18][CH:17]=1.[NH4+].[Cl-]>C1COCC1>[Br:15][C:16]1[C:25]2[CH2:24][CH2:23][CH2:22][C:21]([C:2]3[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([CH3:9])[CH:3]=3)([OH:26])[C:20]=2[CH:19]=[N:18][CH:17]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 4-bromo-1,2-dimethylbenzene (78.6 mg, 425 μmol) in THF (1.3 mL) was cooled (−78° C.) and treated with n-BuLi (1.6 M in n-hexane, 265 μL, 425 μmol). After 15 min a solution of 4-bromo-6,7-dihydroisoquinolin-8(5H)-one (intermediate A-1[C]) (80 mg, 354 μmol) in THF (1.3 mL) was added and after 1 h the brown suspension was warmed up 0° C. The mixture was poured on aq. sat. NH4Cl-solution and extracted with EtOAc (3×). The organic layers were washed with aq. sat. NaHCO3 and aq. sat. NaCl solution, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 2%)) gave the title compound (75 mg, 64%) as off-white foam. MS: 332.1 (M+H+, 1 Br).

Workup

extractionextracted with EtOAc (3×)
washThe organic layers were washed with aq. sat. NaHCO3 and aq. sat. NaCl solution
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH (1 to 2%))

Sources & evidence

ORD record: ord-4ae8b7860039466bb129a7a5c10c46cf
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187429B2

Linked notes

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