Acetonitrile → 2-(1-(Methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-((1-((1-(trifluoromethyl)cyclopropyl)methyl)piperidin-4-yl)methoxy)pyridine

HRID 222597Notes

Reaction equation

HRID 222597 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH2:23][CH2:24][N:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:26][CH:27]=3)=C[C:17]=2F)[CH2:10][CH2:9]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].C(#[N:41])C.CS(O[CH2:47][C:48]1([C:51]([F:54])([F:53])[F:52])[CH2:50][CH2:49]1)(=O)=O>ClCCl.O>[CH3:31][S:28]([N:25]1[CH2:26][CH:27]=[C:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([CH2:47][C:48]4([C:51]([F:52])([F:53])[F:54])[CH2:49][CH2:50]4)[CH2:9][CH2:10]3)=[CH:17][N:41]=2)[CH2:23][CH2:24]1)(=[O:30])=[O:29]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 668644984-[2-Fluoro-4-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-phenoxymethyl]-piperidine-1-carboxylic acid tert-butyl esterHCID 86649942(1-(Trifluoromethyl)cyclopropyl)methyl methanesulfonate

Product 1

HCID 581111522-(1-(Methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-((1-((1-(trifluoromethyl)cyclopropyl)methyl)piperidin-4-yl)methoxy)pyridineYield 65.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

To Preparation 6 (206 mg, 0.586 mmol), potassium carbonate (243 mg, 1.76 mmol) and acetonitrile (2.93 mL, 56 mmol) in a microwave vial is added (1-(trifluoromethyl)cyclopropyl)methyl methanesulfonate (256 mg, 1.17 mmol). The microwave vial is sealed and heated at 140° C. for 2 h then 150° C. for 30 min in the Biotage microwave. The reaction is diluted with dichloromethane and water. The organic layer is separated and washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue is triturated with diethylether and the title product is collected via vacuum filtration to obtain 0.181 g of the title compound. MS (m/z) 474 (M+1).

Workup

  1. customThe microwave vial is sealed
  2. customThe organic layer is separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is triturated with diethylether
  8. filtrationthe title product is collected via vacuum filtration

Sources & evidence

ORD record
ord-e3b419b5ca9c479392ca8f560c5c9e17
Source dataset
uspto-grants-2012_06
Patent number
US08207344B2

Reaction notes

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