Sodium hydride → 4-(Isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1930201Notes

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][CH:27]=1)[CH:24]=[N:23][CH:22]=[CH:21]2>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][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

7.49 g of 4-hydroxy-piperidine-1-carboxylic acid-tert-butylester were dissolved in 20 mL of dry dimethyl acetamide. 1.49 g of sodium hydride (60%) were added. Then a solution of 3.65 g of 6-fluoroisoquinoline (3) in dimethyl acetamide was added dropwise. The solution was heated at 80° C. for 2 hours, then the solvent was removed and the residue was taken up in dichloromethane. The organic layer was extracted twice with water and then with brine, dried over magnesium sulfate and evaporated to dryness. The crude product was purified by silica gel chromatography to yield 6.22 g of 4-(isoquinolin-6-yloxy)-piperidine-1-carboxylic acid-tert-butylester (7). Rt=1.32 min (Method B). Detected mass: 329.1 (M+H+).

Workup

customthe solvent was removed
extractionThe organic layer was extracted twice with water
dry with materialwith brine, dried over magnesium sulfate
customevaporated to dryness
customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record: ord-91c5290c793b4cf9826c256bccc7972a
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188117B2

Reaction notes

Loading…