Triethyl phosphonoacetate → HCID 19348612, compound

HRID 1637550Notes

Reaction equation

HRID 1637550 reaction equation
C(OP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[H-].[Na+].[C:17]([C:21]1[CH:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][C:22]=1[NH:29][C:30](=[O:48])[CH2:31][CH:32]([C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[C:39]=1[O:46][CH3:47])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH3:20])([CH3:19])[CH3:18]>CN(C)C=O.C(OCC)(=O)C>[C:17]([C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:23][C:22]=1[NH:29][C:30](=[O:48])[CH2:31][CH:32]([C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[C:39]=1[O:46][CH3:47])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH3:18])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 19348712HCID 19348712, compound

Product 1

HCID 19348612HCID 19348612, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1.23 ml (6.22 mmol) of ethyl diethylphosphonoacetate were added dropwise, whilst ice-cooling, over a period of 3 minutes to a suspension of 271 mg (6.22 mmol) of sodium hydride (as a 55% w/w dispersion in mineral oil) in 7 ml of dimethylformamide, and the resulting mixture was then stirred at room temperature for 30 minutes. A solution of 1.37 g (3.11 mmol) of N-(2-t-butyl-5-formylphenyl)-3-(2,3-dimethoxyphenyl)octanamide (prepared as described in Preparation 24), in 6 ml of dimethylformamide was ice-cooled and then added dropwise to the mixture over a period of 3 minutes. The resulting mixture was stirred at room temperature for 1.5 hours. At the end of this time, the reaction mixture was diluted with ethyl acetate, and the diluted solution was washed with water and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. A solution of the residue in 20 ml of ethanol was stirred at room temperature for 8 hours in an atmosphere of hydrogen and in the presence of 400 mg of 10% palladiun-on-charcoal. At the end of this time, the reaction mixture was filtered using a Celite (trade mark) filter aid to remove the catalyst, and the filtrate was freed from the solvent by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel, using a 2:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 1.56 g (yield 98%) of the title compound as an oily substance.

Workup

  1. temperaturecooled
  2. additionadded dropwise to the mixture over a period of 3 minutes
  3. stirringThe resulting mixture was stirred at room temperature for 1.5 hours
  4. washthe diluted solution was washed with water and with a saturated aqueous solution of sodium chloride, in that order
  5. dry with materialafter which it was dried over anhydrous magnesium sulfate
  6. customthe solvent was removed by distillation under reduced pressure
  7. stirringA solution of the residue in 20 ml of ethanol was stirred at room temperature for 8 hours in an atmosphere of hydrogen and in the presence of 400 mg of 10% palladiun-on-charcoal
  8. filtrationAt the end of this time, the reaction mixture was filtered
  9. filtrationfilter aid
  10. customto remove the catalyst
  11. distillationthe filtrate was freed from the solvent by distillation under reduced pressure
  12. customThe resulting residue was purified by column chromatography through silica gel
  13. additionby volume mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-d7c32027d0574b55bef96479d8db1d99
Source dataset
uspto-grants-2000_03
Patent number
US06040339

Reaction notes

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