Diisopropyl Ether → tert-Butyl 4-(2-(5-bromo-3-(trifluoromethyl)pyridin-2-yloxy)ethyl)piperidine-1-carboxylate

HRID 522276Notes

Reaction equation

HRID 522276 reaction equation
[OH:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Br:35][C:36]1[CH:37]=[C:38]([C:43]([F:46])([F:45])[F:44])[C:39](O)=[N:40][CH:41]=1.C(P(CCCC)CCCC)CCC.C(OC(C)C)(C)C>C1(C)C=CC=CC=1>[Br:35][C:36]1[CH:37]=[C:38]([C:43]([F:46])([F:44])[F:45])[C:39]([O:1][CH2:2][CH2:3][CH:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]2)=[N:40][CH:41]=1

Participants

7

Reactant 5

HCID 7914Diisopropyl EtherHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidineHCID 178517592HCID 178517592, compound

Product 1

HCID 69931589tert-Butyl 4-(2-(5-bromo-3-(trifluoromethyl)pyridin-2-yloxy)ethyl)piperidine-1-carboxylateYield 68.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

tert-Butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate (7.7 g) and 1,1′-(azodicarbonyl)dipiperidine (11.6 g) were added to a mixture of 5-bromo-3-(trifluoromethyl)pyridine-2-ol (7 g) and toluene (124 mL) at room temperature. Tributylphosphine (11.6 mL) was added thereto under ice-cooling, and the mixture was stirred at room temperature overnight. After diisopropylether was added to the reaction mixture, the mixture was stirred, and the insoluble material was separated by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (Hex:EtOAc=100:0 to 70:30), whereby tert-butyl 4-(2-{[5-bromo-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate (8.93 g) was obtained as a colorless oil.

Workup

  1. temperatureunder ice-cooling
  2. stirringthe mixture was stirred
  3. customthe insoluble material was separated by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (Hex:EtOAc=100:0 to 70:30)

Sources & evidence

ORD record
ord-487b8ec39c8841549b5dafae939f54fe
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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