Sodium hydride → HCID 66876443, compound

HRID 1666460Notes

Reaction equation

HRID 1666460 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([CH:16]=[C:17]([O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=2)[CH:18]=1)[CH2:7]P(=O)(OCC)OCC.O=[C:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]1>C1COCC1>[Br:3][C:4]1[CH:5]=[C:6]([CH:16]=[C:17]([O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][N:21]=2)[CH:18]=1)[CH:7]=[C:31]1[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86623908Diethyl 3-bromo-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylphosphonate

Product 1

HCID 66876443HCID 66876443, compoundYield 101.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (0.292 g, 12.17 mmol) in THF (10 mL) under inert atmosphere cooled to 0° C. was added diethyl 3-bromo-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylphosphonate (3.8 g, 8.11 mmol) as a solution in THF (10 mL) dropwise. The reaction was stirred for 30 min at 0° C. and tert-butyl 4-oxopiperidine-1-carboxylate (1.62 g, 8.11 mmol) was added as a solution in THF (10 mL). The reaction was stirred at RT for 5 h. The reaction mixture was cooled to 0° C. and quenched with saturated aqueous NH4Cl. The mixture was extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4, and evaporated to dryness to give the title compound (4.22 g, 100%). 1H NMR (500 MHz, CDCl3): δ 8.44 (s, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.22 (s, 1H), 7.18 (s, 1H), 7.03 (d, J=8.5 Hz, 1H), 6.91 (s, 1H), 6.28 (s, 1H), 3.49 (m, 2H), 3.40 (m, 2H), 2.44 (m, 2H), 2.32 (m, 2H), 1.47 (s, 9H); m/z (513.2, 515.2, M+ H+).

Workup

  1. stirringThe reaction was stirred at RT for 5 h
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with saturated aqueous NH4Cl
  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

Sources & evidence

ORD record
ord-27e90df69de4418ca429a655eeaaf24b
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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