Sodium hydride → HCID 86757409, compound

HRID 1596711Notes

Reaction equation

HRID 1596711 reaction equation
[H-].[Na+].[CH2:3]([N:5]([CH2:17][CH3:18])[C:6](=[O:16])[CH2:7]P(=O)(OCC)OCC)[CH3:4].[F:19][C:20]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:21]=1[CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=O)[CH3:31])=[CH:26][C:25]=1[O:33][CH2:34][CH2:35][CH2:36][O:37][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][O:39]1>C1COCC1>[CH2:17]([N:5]([CH2:3][CH3:4])[C:6](=[O:16])/[CH:7]=[C:30](/[C:27]1[CH:28]=[CH:29][C:24]([O:23][CH2:22][C:21]2[C:20]([F:19])=[CH:47][CH:46]=[CH:45][C:44]=2[F:48])=[C:25]([O:33][CH2:34][CH2:35][CH2:36][O:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][O:39]2)[CH:26]=1)\[CH3:31])[CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13124144HCID 13124144, compoundHCID 21702655HCID 21702655, compound

Product 1

HCID 86757409HCID 86757409, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of washed NaH (0.74 g, 30.94 mmol)) in THF (30 mL) is added a solution of diethyl [2-(diethylamino)-2-oxoethyl]-phosphonate (7.77 g, 30.94 mmol) in THF (30 mol), dropwise, and the solution is stirred at room temperature for 5 minutes until gas evolution ceases. A solution of 4′-(2,6-difluorobenzyloxy)-3′-[3-(tetrahydropyran-2-yloxy)-propoxy]-acetophenone (6.50 g, 15.47 mmol) in THF (30 mL) is then added over 5 minutes and the resulting mixture is refluxed for 18 hours. After cooling, the mixture is quenched with 30 mL saturated aqueous NH4Cl, and is concentrated to 30 mL in vacuo. The residue is dissolved in EtOAc (50 mL), washed with H2O (1×50 mL) and brine (1×50 ml), dried over MgSO4, and concentrated in vacuo. Chromatography (silica, 3:1 hexane/EtOAc) provides N,N-diethyl (E)-3-{4-(2,6-difluorobenzyloxy)-3-[3-(tetrahydropyran-2-yloxy)-propoxy]-phenyl}-2-butenamide.

Workup

  1. temperaturethe resulting mixture is refluxed for 18 hours
  2. temperatureAfter cooling
  3. customthe mixture is quenched with 30 mL saturated aqueous NH4Cl
  4. concentrationis concentrated to 30 mL in vacuo
  5. dissolutionThe residue is dissolved in EtOAc (50 mL)
  6. washwashed with H2O (1×50 mL) and brine (1×50 ml)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-548118f5afe14cd6828d8d441fbf5fbc
Source dataset
uspto-grants-2001_09
Patent number
US06291530B1

Reaction notes

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