Water → 1,1-Dimethylethyl 4-[(6-chloro-8-quinolinyl)oxy]-1-piperidinecarboxylate

HRID 1363004Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10](F)[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[OH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.CC(C)([O-])C.[Na+].O>CN1C(=O)CCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:13][CH:14]3[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]3)[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2

Participants

Conditions

Temperature: 140 °C

Procedure

6-Chloro-8-fluoroquinoline (for example, as prepared for Intermediate 5) (2.18 g, 12 mmol) was dissolved in NMP (20 ml) and treated with 1,1-dimethylethyl 4-hydroxy-1-piperidinecarboxylate (commercially available, for example, from Acros and/or Aldrich) (4.85 g, 24 mmol) and sodium tert-butoxide (2.38 g, 25 mmol). Further NMP was added (5 ml) and the resulting mixture was stirred at 140° C. for 1 h, and then allowed to cool overnight. The reaction mixture was treated with water and extracted with toluene. The organic extract was washed with water (×3), dried (MgSO4), and concentrated in vacuo. The residue was purified by silica chromatography (2×70 g), eluting with 0-100% EtOAc-cyclohexane over 30 min. The relevant fractions were concentrated in vacuo to give the title compound as a yellow gum (2.73 g, 63%): LCMS RT=3.37 min, ES+ve m/z 363/365 [M+H]+.

Workup

temperatureto cool overnight
extractionextracted with toluene
extractionThe organic extract
washwas washed with water (×3)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe residue was purified by silica chromatography (2×70 g)
washeluting with 0-100% EtOAc-cyclohexane over 30 min
concentrationThe relevant fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-31c5a85782b8458c83bd4fd4ac5f80db
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07884114B2

Reaction notes

Loading…