Water → 4-[2-(4-Methoxy-benzyl)-7-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1930207Notes

Reaction equation

HRID 1930207 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[CH3:28])[C:24](=[O:29])[N:23]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)[CH:22]=[CH:21]2.O>CC(N(C)C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][C:27]=2[CH3:28])[C:24](=[O:29])[N:23]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)[CH:22]=[CH:21]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 592260436-fluoro-2-(4-methoxybenzyl)-7-methylisoquinolin-1(2H)-one

Product 1

HCID 674579744-[2-(4-Methoxy-benzyl)-7-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl esterYield 88.6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of 3.2 g (15.9 mmol) 1-tert-butoxycarbonyl-4-hydroxypiperidine in 110 mL dimethylacetamide was stirred with 1.36 g (45.4 mmol) of 80-% sodium hydride for 1 h at room temperature. Then a suspension of 4.5 g (15.1 mmol) of 6-fluoro-2-(4-methoxy-benzyl)-7-methyl-2H-isoquinolin-1-one in dimethylacetamide was added. The reaction mixture was heated to 80° C. for 2 h during which time a clear solution was obtained. The reaction mixture was slowly added to 160 mL water and after 1 h of stirring the product was isolated by filtration and dried over night in vacuum. 6.4 g of 4-[2-(4-Methoxy-benzyl)-7-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester were obtained.

Workup

  1. additionwas added
  2. customwas obtained
  3. customwas isolated by filtration
  4. customdried over night in vacuum

Sources & evidence

ORD record
ord-dd3b2ba9860543f1bb46e5276793c3f4
Source dataset
uspto-grants-2012_05
Patent number
US08188117B2

Reaction notes

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