Acetic Acid → Dimethyl [3-(3-chlorophenyl)-2-oxopropyl]phosphonate

HRID 1267462Notes

Reaction equation

HRID 1267462 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.C[O:14][C:15](=O)[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1.C(O)(=O)C>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:15](=[O:14])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1)(=[O:7])[O:5][CH3:6]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 12958Dimethyl methylphosphonateHCID 2733544Methyl 2-(3-chlorophenyl)acetateHCID 178418339Butyllithium

Product 1

HCID 12989750Dimethyl [3-(3-chlorophenyl)-2-oxopropyl]phosphonateYield 23.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of dimethyl methylphosphonate (17.93 g, 144 mmol) in THF (270 mL) at −78° C. was slowly added n-BuLi (2.5M, 64.2 mL, 160.6 mmol). The reaction mixture was stirred for 1 h and (3-chloro-phenyl)-acetic acid methyl ester (26.93 g, 146 mmol) was slowly added. The reaction mixture was allowed to warm to room temperature and was stirred for 24 h. Acetic acid (15 mL) was added and the volatiles were removed in vacuo. The residue was diluted with CH2Cl2 and the organic solution was washed carefully with saturated aqueous NaHCO3 (3 times). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification by medium pressure chromatography (20% EtOAc in hexanes to EtOAc) provided the title compound (9.28 g).

Workup

  1. customat −78° C.
  2. stirringwas stirred for 24 h
  3. customthe volatiles were removed in vacuo
  4. additionThe residue was diluted with CH2Cl2
  5. washthe organic solution was washed carefully with saturated aqueous NaHCO3 (3 times)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by medium pressure chromatography (20% EtOAc in hexanes to EtOAc)

Sources & evidence

ORD record
ord-b7e975de932444f0a985d79fbff73b28
Source dataset
uspto-grants-2003_04
Patent number
US06552067B2

Reaction notes

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