Ethyl diethoxyacetate → HCID 178471714, compound

HRID 920855

Reaction equation

HRID 920855 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8].[CH2:12]([O:14][CH:15]([O:21][CH2:22][CH3:23])[C:16](OCC)=[O:17])[CH3:13].[Li+].CC([N-]C(C)C)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[O:11])/[CH:10]=[C:16](\[OH:17])/[CH:15]([O:21][CH2:22][CH3:23])[O:14][CH2:12][CH3:13])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 80169Ethyl diethoxyacetateHCID 5204223'-Chloro-4'-fluoroacetophenoneHCID 2724682Lithium diisopropylamide

Product 1

HCID 178471714HCID 178471714, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −78° C. solution of 1-(3-chloro-4-fluorophenyl)ethanone (16.25 g, 94 mmol) and ethyl 2,2-diethoxyacetate (20.73 mL, 113 mmol) in THF (392 mL) was added, dropwise, a solution of LDA (51.8 mL, 104 mmol, 2M in THF). The resultant reaction mixture was gradually allowed to reach room temperature and continued stirring for 16 h. The reaction was carefully quenched with water and diluted with EtOAc. The two layers were separated and the aq. layer was extracted with EtOAc (2×150 mL) The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered and the filtrate was concentrated under reduced pressure to provide a crude oil. It was purified by silica gel chromatography (1500 g Commodity column, eluting with a 10% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate A39A (9.97 g, 35%) as a solid. MS(ES): m/z=257 [M-OEt]+.

Workup

  1. customThe resultant reaction mixture
  2. customto reach room temperature
  3. customThe reaction was carefully quenched with water
  4. additiondiluted with EtOAc
  5. customThe two layers were separated
  6. extractionthe aq. layer was extracted with EtOAc (2×150 mL) The combined organic layer
  7. washwas washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customto provide a crude oil
  12. customIt was purified by silica gel chromatography (1500 g Commodity column
  13. washeluting with a 10% EtOAc in hexanes)
  14. additionFractions containing the product
  15. customevaporated
  16. customto afford Intermediate A39A (9.97 g, 35%) as a solid

Sources & evidence

ORD record
ord-64868f37ea864363897c8a57e044ad9c
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Linked notes

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