4-tert-Butylphenylboronic acid → 6-(4-tert-butyl-phenoxy)-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester

HRID 1984817Notes

Reaction equation

HRID 1984817 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([OH:15])[CH:12]=2)[CH2:7][N:6]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:4].[C:23]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24]>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:15][C:30]3[CH:31]=[CH:32][C:27]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:28][CH:29]=3)[CH:12]=2)[CH2:7][N:6]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:4]

Participants

5

Reactant 2

HCID 27343204-tert-Butylphenylboronic acidHCID 577645552-tert-Butyl 3-methyl 6-hydroxy-3,4-dihydroisoquinoline-2,3(1H)-dicarboxylate

Product 1

HCID 671180436-(4-tert-butyl-phenoxy)-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl esterYield 49.2%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

6-Hydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (0.5 g, 1.62 mmol) in DCM (15 mL) was treated with copper acetate (0.59 g, 3.3 mmol), 4-tert-butylphenylboronic acid (0.87 g, 4.8 mmol), and TEA (1.0 mL, 7.9 mmol) by the general procedure G. The crude product was purified by flash column chromatography on silica gel using Hexanes:EtOAc (70:30) to give 0.35 g of 6-(4-tert-butyl-phenoxy)-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester which was deprotected using general procedure N to give 6-(4-tert-butyl-phenoxy)-1,2,3,4-tetrahydro-isoquinoline-(3S)-carboxylic acid methyl ester hydrochloride salt (0.27 g).

Workup

  1. customThe crude product was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-1c8da13226994f1c917c23e88313c587
Source dataset
uspto-grants-2009_06
Patent number
US07544699B2

Reaction notes

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