Trifluoroacetic acid → 2-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid

HRID 56758Notes

Reaction equation

HRID 56758 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:34]#[N:35])=[C:13]([C:15]2[C:20]([O:21][CH3:22])=[CH:19][N:18]([CH:23]([CH2:31][CH3:32])[C:24]([O:26]C(C)(C)C)=[O:25])[C:17](=[O:33])[CH:16]=2)[CH:14]=1>ClCCl>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:34]#[N:35])=[C:13]([C:15]2[C:20]([O:21][CH3:22])=[CH:19][N:18]([CH:23]([CH2:31][CH3:32])[C:24]([OH:26])=[O:25])[C:17](=[O:33])[CH:16]=2)[CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid3×HCID 117622718tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoate

Product 1

HCID 1176225692-[4-(5-Chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under argon and at RT, 7.8 ml (101.8 mmol, 10 eq.) of trifluoroacetic acid were added to a solution of 4.1 g (10.2 mmol) of tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoate (racemate) in 40 ml of dichloromethane, the mixture was stirred at RT for 1 h, a further 7.8 ml (101.8 mmol, 10 eq.) of trifluoroacetic acid were added, the mixture was stirred at RT for 1 h, a further 7.8 ml (101.8 mmol, 10 eq.) of trifluoroacetic acid were added and the mixture was stirred at RT for 1 h. Once the reaction had gone to completion, the reaction mixture was concentrated under reduced pressure and the residue was co-evaporated in each case three times with dichloromethane and once with toluene and dried under reduced pressure. The residue was taken up in 100 ml of ethyl acetate and washed repeatedly with a strongly diluted aqueous sodium bicarbonate solution (where the pH of the washing water should not exceed pH 3-4 since otherwise the product is well soluble in water). The organic phase was subsequently dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was triturated with methyl tert-butyl ether, filtered, washed twice with methyl tert-butyl ether and dried under reduced pressure. Yield: 2.9 g (83% of theory)

Workup

  1. stirringthe mixture was stirred at RT for 1 h
  2. stirringthe mixture was stirred at RT for 1 h
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. customdried under reduced pressure
  5. washwashed repeatedly with a strongly diluted aqueous sodium bicarbonate solution (where the pH of the washing water should not
  6. dry with materialThe organic phase was subsequently dried (sodium sulphate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with methyl tert-butyl ether
  10. filtrationfiltered
  11. washwashed twice with methyl tert-butyl ether
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-24a37dabda38429a957e25af76696b28
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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