tert-Butyl piperazine-1-carboxylate → 4-[2-(2-Hydroxy-ethyl)-1-oxo-1,2-dihydro-isoquinolin-7-yl]piperazine-1-carboxylic acid tert-butyl ester

HRID 2068594Notes

Reaction equation

HRID 2068594 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([CH2:13][CH2:14][OH:15])[C:9]2=[O:12])=[CH:4][CH:3]=1.[N:16]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:25]([O:24][C:22]([N:16]1[CH2:21][CH2:20][N:19]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][N:8]([CH2:13][CH2:14][OH:15])[C:9]3=[O:12])=[CH:4][CH:3]=2)[CH2:18][CH2:17]1)=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23665647Potassium tert-butoxideHCID 592382027-Bromo-2-(2-hydroxyethyl)-isoquinolin-1-one

Product 1

HCID 592381654-[2-(2-Hydroxy-ethyl)-1-oxo-1,2-dihydro-isoquinolin-7-yl]piperazine-1-carboxylic acid tert-butyl esterYield 64.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of compound 6 (6.8 g, 25.4 mmol), tert-butyl piperazine-1-carboxylate (5.68 g, 30.5 mmol), Pd2(dba)3 (775 mg, 0.85 mmol), S-Phos (1.16 g) and t-BuOK (5.7 g, 50.8 mmol) in toluene (100 mL) was heated to 90° C. under nitrogen overnight. Then the mixture was cooled to room temperature and filtered. The filtrate was concentrated, the residue was dissolved in methylene chloride, washed with water, dried (sodium sulfate), concentrated and purified by flash column chromatography (silica gel) to give 7 (6.1 g, 64%)

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. dissolutionthe residue was dissolved in methylene chloride
  4. washwashed with water
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated
  7. custompurified by flash column chromatography (silica gel)

Sources & evidence

ORD record
ord-bb9add7ce3014d93859927942e6edd2f
Source dataset
uspto-grants-2012_10
Patent number
US08299023B2

Reaction notes

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