6-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one → [2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-acetic Acid Tert-Butyl Ester

HRID 41905Notes

Reaction equation

HRID 41905 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH2:6][CH2:5]2.[Cl-].[C:23]([O:27][C:28](=[O:31])[CH2:29][Zn+])([CH3:26])([CH3:25])[CH3:24]>C1COCC1.CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[C:23]([O:27][C:28](=[O:31])[CH2:29][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH2:6][CH2:5]2)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 2

HCID 592164816-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-oneHCID 178451183HCID 178451183, compound

Product 1

HCID 59216409[2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-acetic Acid Tert-Butyl EsterYield 95.6%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst2×HCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

6-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1one(1.9 g, 5.5 mmole), Q-phos (0.0632 g, 0.11 mmole) and Pd(dba)2 (0.0781 g, 0.11 mmole) in 10 ml THF were added to 2-tert-butoxy-2-oxoethylzinc chloride 15 ml (0.55 M) under argon. The reaction mixture was stirred at room temperature for 16 hours. Next a third of the initial amount of Q-phos, Pd(dba)2 and zinc enolate were added and the mixture heated for 1 hour at 70° C. to bring the reaction to completion. The desired product (2 g ; 95.6% yield) was isolated by flash chromatography using silica gel column chromatography with 10% -40% ethylacetate in hexane as eluent.

Workup

  1. temperaturethe mixture heated for 1 hour at 70° C.
  2. customthe reaction to completion

Sources & evidence

ORD record
ord-0454455b4ef147a38b95bb0385b714c7
Source dataset
uspto-grants-2013_09
Patent number
US08536166B2

Reaction notes

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