Cesium carbonate → tert-Butyl 4-(3-(5-(2,2,2-trifluoroethoxy)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

HRID 1666414Notes

Reaction equation

HRID 1666414 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:10]=[C:11]([CH:26]=[CH:27][CH:28]=2)[CH:12]=[C:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[N:6][CH:7]=1.[F:29][C:30](I)([F:32])[F:31].[C:34]([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[F:29][C:30]([F:32])([F:31])[CH2:34][O:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:10]=[C:11]([CH:26]=[CH:27][CH:28]=2)[CH:12]=[C:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:15][CH2:14]2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 16843TrifluoroiodomethaneHCID 66875736tert-Butyl 4-(3-(5-hydroxypyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

Product 1

HCID 66875845tert-Butyl 4-(3-(5-(2,2,2-trifluoroethoxy)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylateYield 37.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of tert-butyl 4-(3-(5-hydroxypyridin-2-yloxy)benzylidene)piperidine-1-carboxylate (0.8 g, 2.09 mmol) in DMF (5 mL) cooled to 0° C. was added trifluoromethyliodide (548.9 mg, 2.614 mmol) and Cs2CO3 (1.3 gm, 4.18 mmol). The reaction mixture was stirred at 80° C. overnight. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate three times. The organic layer was washed with water and brine solution, dried over Na2SO4 and concentrated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (1:19 acetone:hexane) to give the title compound (360 mg, 37%). 1H NMR (500 MHz, CDCl3): δ 7.91 (d, J=2.8 Hz, 1H), 7.31 (m, 2H), 7.0 (d, J=7.75 Hz, 1H), 6.89 (m, 3H), 6.33 (s, 1H), 4.33 (q, J=8 Hz, 2H), 3.49 (m, 2H), 3.39 (m, 2H), 2.45 (m, 2H), 2.31 (m, 2H), 1.47 (s, 9H); m/z (465.1, M+ H+).

Workup

  1. extractionextracted with ethyl acetate three times
  2. washThe organic layer was washed with water and brine solution
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (1:19 acetone:hexane)

Sources & evidence

ORD record
ord-d6c9ecc9debf4ff29b7bcf3d496fda45
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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