Sodium hydride → Tert-butyl 4-(3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

HRID 1666465Notes

Reaction equation

HRID 1666465 reaction equation
[H-].[Na+].[CH:3]1([C:6]2[CH:7]=[C:8]([CH:18]=[C:19]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][N:23]=3)[CH:20]=2)[CH2:9]P(=O)(OCC)OCC)[CH2:5][CH2:4]1.[C:32]([N:39]1[CH2:44][CH2:43][CH2:42][CH2:41][C:40]1=O)([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH:3]1([C:6]2[CH:7]=[C:8]([CH:18]=[C:19]([O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][N:23]=3)[CH:20]=2)[CH:9]=[C:42]2[CH2:43][CH2:44][N:39]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:40][CH2:41]2)[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 86623909HCID 86623909, compound

Product 1

HCID 66875428Tert-butyl 4-(3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)piperidine-1-carboxylateYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (0.11 g, 4.65 mmol) in dry THF (1.5 mL) under an inert atmosphere cooled to 0° C. was added diethyl 3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylphosphonate (0.8 g, 1.86 mmol) as a solution in THF (6 mL). The mixture was stirred for 30 min at 0° C. N-Boc piperidone (0.37 g, 1.86 mmol) was added as a solution in THF (3 mL) and the mixture was stirred at RT for 5 h. The reaction was cooled to 0° C. and quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel column chromatography (10% ethyl acetate in hexane) to give the title compound (0.408 g, 46%). 1H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.87 (d, J=8 Hz, 1H), 6.97 (d, J=8.5 Hz, 1H), 6.79 (s, 1H), 6.74 (s, 1H), 6.68 (s, 1H), 6.30 (s, 1H), 3.49 (m, 2H), 3.39 (m, 2H), 2.45 (m, 2H), 2.31 (m, 2H), 1.88 (m, 1H), 1.46 (s, 9H), 0.96 (d, J=8.5 Hz, 2H), 0.69 (d, J=4.5 Hz, 2H); m/z (475.1, M+ H+).

Workup

  1. stirringthe mixture was stirred at RT for 5 h
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with saturated aqueous ammonium chloride
  4. extractionThe mixture was extracted with ethyl acetate three times
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customThe residue was purified by silica gel column chromatography (10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-60c50977a40340e9b66a1711c95df9b1
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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