Dichloromethane methanol → 4-(4-Amino-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 729608Notes

Reaction equation

HRID 729608 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([N+:25]([O-])=O)=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.ClCCl>C1COCC1.C(O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([NH2:25])=[CH:17][N:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 21226129Dichloromethane methanolHCID 69053768HCID 69053768, compound

Product 1

HCID 578328234-(4-Amino-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl esterYield 98.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of 4-(4-nitro-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (33.5 g, 89.7 mmol) in THF (300 mL) and ethanol (300 mL) add 10% Pd/C (1.80 g, 1.69 mmol) as a slurry in ethanol (25 mL). Place the mixture in a Parr shaker under hydrogen atmosphere (25-40 psi) at room temperature for 8 hours. Filter the mixture through a pad of diatomaceous earth and wash with ethanol until the filtrate is colorless. Concentrate the filtrate under reduced pressure to give dark oil. Subject residue to silica gel chromatography eluting with 1% then 2.5% MeOH/dichloromethane to afford the title compound (30.3 g, 98% yield) as an orange glass. (ES+): m/z 344 (M++H).

Workup

  1. customat room temperature
  2. customfor 8 hours
  3. filtrationFilter the mixture through a pad of diatomaceous earth
  4. washwash with ethanol until the filtrate
  5. concentrationConcentrate the filtrate under reduced pressure
  6. customto give dark oil
  7. washSubject residue to silica gel chromatography eluting with 1%

Sources & evidence

ORD record
ord-3bc3165130b74abda4c7201d6843e3aa
Source dataset
uspto-grants-2009_09
Patent number
US07582638B2

Reaction notes

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