Diisopropylethylamine → (S)-3-(2,5-difluoro-4-(methyl-sulfonyl)phenoxy)-1'-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-[1,4'-bipiperidin]-2-one

HRID 408027Notes

Reaction equation

HRID 408027 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[C:19]([F:26])=[CH:18][C:3]=1[O:4][C@H:5]1[CH2:10][CH2:9][CH2:8][N:7]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[C:6]1=[O:17].F[C:28]1[C:33]([F:34])=[CH:32][C:31]([C:35]([F:38])([F:37])[F:36])=[CH:30][N:29]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[C:19]([F:26])=[CH:18][C:3]=1[O:4][C@H:5]1[CH2:10][CH2:9][CH2:8][N:7]([CH:11]2[CH2:16][CH2:15][N:14]([C:28]3[C:33]([F:34])=[CH:32][C:31]([C:35]([F:38])([F:36])[F:37])=[CH:30][N:29]=3)[CH2:13][CH2:12]2)[C:6]1=[O:17]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 134215472,3-Difluoro-5-(trifluoromethyl)pyridineHCID 66802663(S)-3-(2,5-Difluoro-4-(methylsulfonyl)phenoxy)-1,4'-bipiperidin-2-one

Product 1

HCID 86688124(S)-3-(2,5-difluoro-4-(methyl-sulfonyl)phenoxy)-1'-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-[1,4'-bipiperidin]-2-oneYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-[1,4′-bipiperidin]-2-one (Preparation G; 30 mg, 0.077 mmol) in DMF was added 2,3-difluoro-5-(trifluoromethyl)pyridine (42 mg, 0.23 mmol) and DIEA (30 μL, 0.23 mmol) and the reaction was stirred at ambient temperature for 18 hours. The reaction was diluted with EtOAc and washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative TLC (EtOAc/DCM 4:1) to give (S)-3-(2,5-difluoro-4-(methyl-sulfonyl)phenoxy)-1′-(3-fluoro-5-(trifluoromethyl)pyridin-2-yl)-[1,4′-bipiperidin]-2-one as a white solid (20 mg, 0.035 mmol, 46% yield). Mass spectrum (apci) m/z=552.2 (M+H).

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative TLC (EtOAc/DCM 4:1)

Sources & evidence

ORD record
ord-7c34d6fcf58e421d92f0b8c858b77219
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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