Trifluoroacetic acid → 7-Methyl-6-(piperidin-4-yloxy)-2h-isoquinolin-1-one

HRID 1930208Notes

Reaction equation

HRID 1930208 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2[CH3:25])[C:21](=[O:26])[N:20](CC2C=CC(OC)=CC=2)[CH:19]=[CH:18]3)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>>[CH3:25][C:24]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][NH:20][C:21]2=[O:26])=[CH:16][C:15]=1[O:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 674579744-[2-(4-Methoxy-benzyl)-7-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 576525087-Methyl-6-(piperidin-4-yloxy)-2h-isoquinolin-1-one

Conditions

Temperature
150 °C

Procedure

6.4 g (13.4 mmol) 4-[2-(4-methoxy-benzyl)-7-methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy]-piperidine-1-carboxylic acid tert-butyl ester were dissolved in 30.5 g (267.4 mmol) trifluoroacetic acid. After 1 h at room temperature the mixture was heated for 2 h in a microwave oven at 150° C. Then the excess trifluoroacetic acid was distilled off in vacuo and the residue was diluted with 130 mL of 1 M hydrochloric acid. The aqueous phase was washed with methylene chloride 3 times and then it was freeze dried to give a hydrochloride, which was crystallized from isopropanol. This furnished 3.2 g 7-methyl-6-(piperidin-4-yloxy)-2H-isoquinolin-1-one (16) as hydrochloride.

Workup

  1. distillationThen the excess trifluoroacetic acid was distilled off in vacuo
  2. additionthe residue was diluted with 130 mL of 1 M hydrochloric acid
  3. washThe aqueous phase was washed with methylene chloride 3 times
  4. customdried

Sources & evidence

ORD record
ord-2bba7191024246598a5620fc9cf6590e
Source dataset
uspto-grants-2012_05
Patent number
US08188117B2

Reaction notes

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