Tert-butyl 4-hydroxypiperidine-1-carboxylate → tert-butyl 4-((6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)pyridazin-3-yl)oxy)piperidine-1-carboxylate

HRID 1027184Notes

Reaction equation

CC(C)([O-])C.[K+].[OH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.Cl[C:22]1[N:23]=[N:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH:38]=[CH:37][CH:36]=[N:35]3)=[CH:30][C:29]=2[O:39][CH3:40])=[CH:26][CH:27]=1>C1COCC1>[CH3:40][O:39][C:29]1[CH:30]=[C:31]([N:34]2[CH:38]=[CH:37][CH:36]=[N:35]2)[CH:32]=[CH:33][C:28]=1[C:25]1[N:24]=[N:23][C:22]([O:7][CH:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]2)=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Potassium tert-butoxide (1.0 M in THF, 0.82 mL, 0.82 mmol) was added to tert-butyl 4-hydroxypiperidine-1-carboxylate (0.17 g, 0.82 mmol) in THF (3 mL) at 0° C. and the mixture was stirred for 10 min at 0° C. 3-Chloro-6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)pyridazine Intermediate 2-1 (0.13 g, 0.45 mmol) was added to the reaction at 0° C. and the mixture was stirred for 1 h at RT. After evaporation under reduced pressure, the crude material was purified by silica chromatography (70 to 100% EtOAc in heptane) to give tert-butyl 4-((6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)pyridazin-3-yl)oxy)piperidine-1-carboxylate (0.18 g, 89%) as a colorless solid.

Workup

stirringthe mixture was stirred for 1 h at RT
customAfter evaporation under reduced pressure
customthe crude material was purified by silica chromatography (70 to 100% EtOAc in heptane)

Sources & evidence

ORD record: ord-399c9d49eb634cec897cf8401a7fd0e8
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729263B2

Reaction notes

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