Triethyl 2-fluoro-2-phosphonoacetate → HCID 86597828, compound

HRID 2180490Notes

Reaction equation

HRID 2180490 reaction equation
C([Li])CCC.[CH3:6][CH2:7][O:8][C:9]([CH:11](P(OCC)(OCC)=O)[F:12])=[O:10].[CH2:21]([C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:36][CH3:37])=[C:30]([C:33](=O)[CH3:34])[CH:31]=2)[O:26][C:25]([CH3:39])([CH3:38])[CH:24]=1)[CH3:22]>C1COCC1>[CH2:21]([C:23]1[C:32]2[C:27](=[CH:28][C:29]([O:36][CH3:37])=[C:30](/[C:33](/[CH3:34])=[C:11](/[F:12])\[C:9]([O:8][CH2:7][CH3:6])=[O:10])[CH:31]=2)[O:26][C:25]([CH3:39])([CH3:38])[CH:24]=1)[CH3:22]

Participants

5

Reactant 3

HCID 2734865Triethyl 2-fluoro-2-phosphonoacetateHCID 22491074HCID 22491074, compound2×HCID 178418339Butyllithium

Product 1

HCID 86597828HCID 86597828, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of n-butyllithium (2.5 M in hexanes, 1.3 mL, 3.28 mmol) in THF (5 mL) at 0° C. was slowly added triethyl-2-fluoro-2-phosphonoacetate (700 mg, 2.89 mmol). The solution was stirred for 10 min at −40° C. The mixture was cooled to −78° C., and a solution of 1-(4-ethyl-7-methoxy-2,2-dimethyl-2H-chromen-6-yl)-ethanone (Compound 53, 222 mg, 0.97 mmol) in THF (5 mL) was added by cannula. After stirring at 0° C. for 4 h, the reaction mixture was quenched with water. The product was extracted with ethyl acetate and the combined extracts were washed with water and brine, and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 10% ethyl acetate in hexane) to produce the title compound as a colorless oil.

Workup

  1. customat 0° C.
  2. temperatureThe mixture was cooled to −78° C.
  3. stirringAfter stirring at 0° C. for 4 h
  4. customthe reaction mixture was quenched with water
  5. extractionThe product was extracted with ethyl acetate
  6. washthe combined extracts were washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationThe solution was filtered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (silica gel, 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8f152e26e73f41a0a0a310c8e464f2c7
Source dataset
uspto-grants-2005_05
Patent number
US06887896B1

Reaction notes

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