Piperidin-4-ol → HCID 9878545, compound

HRID 2199172Notes

Reaction equation

HRID 2199172 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.F[C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([C:17]([F:20])([F:19])[F:18])[CH:10]=1>CS(C)=O>[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([C:17]([F:18])([F:20])[F:19])[CH:10]=2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 79341Piperidin-4-olHCID 6050854-Fluoro-2-(trifluoromethyl)benzonitrile

Product 1

HCID 9878545HCID 9878545, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

2.5 g of 4-hydroxypiperidine and 4.7 g of 4-fluoro-2-(trifluromethyl)-benzonitrile were reacted 5 h at 95° C. in DMSO to form 4-(4-hydroxypiperidin-1-yl)-2-(trifluoromethyl)-benzonitrile which, after aqueous work-up and isolation was disolved in 10 ml DMF was reacted at 5° C. with 250 mg of NaH (60% w/w) for 30 min. Then at 0° C., 2 g of 4,6-dichloropyrimidine were added to the mixture, stirred 30 min at room temperature to form 4-{4-[(6-chloropyrimidin-4-yl)oxy]piperidin-1-yl}-2-(trifluoromethyl)-benzonitrile. 115 mg of isolated by aqueous work-up and isolation by column chromatography were reacted with 138 mg of 1-[4-(trifluoromethyl)-phenyl]piperazine in presence of 117 mg of CsCO3, 7 mg of Pd(OAc)2, 21 mg of RuPhos in 2 ml of tert-BuOH at 85° C. over night to provide compound No. 23 after isolation by aqueous workup and column chromatography.

Sources & evidence

ORD record
ord-c9d04ed7454941fead35a2363d160d39
Source dataset
uspto-grants-2016_06
Patent number
US09357782B2

Reaction notes

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