Sodium hydride → HCID 68557054, compound

HRID 1804853Notes

Reaction equation

HRID 1804853 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]2)=[CH:17][C:16]=1[O:28][CH3:29]>C1COCC1>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:22][CH2:23][C:24](=[CH:7][C:5]([O:4][CH3:3])=[O:6])[CH2:25][CH2:26]2)=[CH:17][C:16]=1[O:28][CH3:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 685574401-(4-Chloro-3-methoxyphenyl)piperidin-4-one

Product 1

HCID 68557054HCID 68557054, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A suspension of 60% dispersion sodium hydride (65.1 mg, 1.627 mmol) in anhydrous THF (2.5 mL) was treated with a solution of trimethyl phosphonoacetate (235 μL, 1.627 mmol) in THF (1 mL) over 5 min. The mixture was stirred at RT for 30 min and then treated with a solution of 1-(4-chloro-3-methoxyphenyl)piperidin-4-one (300 mg, 1.252 mmol) in THF (3 mL). The reaction was stirred at RT for 1 h before it was partitioned between saturated NH4Cl and EtOAc. The extract was dried (Na2SO4) and concentrated to give the crude product, which was purified by flash chromatography (12 g silica gel cartridge and gradient elution from 0 to 30% EtOAc/hexanes) to afford methyl 2-(1-(4-chloro-3-methoxyphenyl)piperidin-4-ylidene)acetate (288 mg, 0.974 mmol, 78% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ ppm 7.19 (1 H, d, J=8.79 Hz), 6.49 (1 H, d, J=2.42 Hz), 6.44 (1 H, dd, J=8.79, 2.64 Hz), 5.73 (1 H, s), 3.88 (3 H, s), 3.70 (3 H, s), 3.26-3.34 (4 H, m, J=5.82, 5.49, 5.33, 5.33 Hz), 3.10 (2 H, t, J=5.38 Hz), 2.45 (2 H, t, J=5.27 Hz).

Workup

  1. stirringThe reaction was stirred at RT for 1 h before it
  2. customwas partitioned between saturated NH4Cl and EtOAc
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by flash chromatography (12 g silica gel cartridge and gradient elution from 0 to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bae56844692246c587ddf4e1eb9b6c64
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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