Acetic Acid → Dimethyl (3,3-dimethyl-2-oxo-4-phenylbutyl)phosphonate

HRID 1288218Notes

Reaction equation

HRID 1288218 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([Li])CCC.[CH3:13][C:14]([CH3:25])([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:15](Cl)=[O:16].C(O)(=O)C>O1CCCC1.CCCCCC>[CH3:13][C:14]([CH3:25])([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:15](=[O:16])[CH2:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 12958Dimethyl methylphosphonateHCID 133072292,2-Dimethyl-3-phenylpropanoyl chlorideHCID 178418339Butyllithium

Product 1

HCID 14302191Dimethyl (3,3-dimethyl-2-oxo-4-phenylbutyl)phosphonate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of dimethyl methylphosphonate (63 g.) in tetrahydrofuran (600 ml.) under nitrogen at -75°, there is added 312 ml. of 1.6 M n-butyl lithium in hexane, while maintaining the temperature below -55°. A solution of 2,2-dimethyl-3-phenylpropionyl chloride (part 2, 48.2 g.) in tetrahydrofuran is added while maintaining the temperature below -60°. The mixture is stirred at that temperature for 2 hrs. and then the temperature is allowed to rise to about 25° C. and the mixture is stirred at that temperature for 16 hrs. Acetic acid (20 ml.) is added, the mixture is concentrated, the residue is shaken with a mixture of diethyl ether-methylene chloride (3:1, v/v) and cold dilute sodium bicarbonate solution. The organic layer is separated, washed with brine, dried and concentrated. The residue is crystallized from diethylether to give the title compound, 62 g.; m.p. 48°-51°; NMR peaks at 7.2, 3.83 and 3.64, 3.28 and 2.9, 2.8 and 1.13 δ.

Workup

  1. temperaturewhile maintaining the temperature below -60°
  2. customto rise to about 25° C.
  3. stirringthe mixture is stirred at that temperature for 16 hrs
  4. concentrationthe mixture is concentrated
  5. stirringthe residue is shaken with a mixture of diethyl ether-methylene chloride (3:1
  6. customThe organic layer is separated
  7. washwashed with brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue is crystallized from diethylether

Sources & evidence

ORD record
ord-bec8d03ac7cb42ae84b63bf32bcc37f5
Source dataset
uspto-grants-1976_10
Patent number
US03987087

Reaction notes

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