Hydrochloric Acid → 6-Methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid

HRID 2089259Notes

Reaction equation

HRID 2089259 reaction equation
[O:1]=[C:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1)[CH2:3][C:4]([O:6]C)=[O:5].CO[CH:21](OC)[CH2:22][C:23](=O)[CH3:24].C[O-].[Na+].[OH-].[Na+].Cl>O.C(O)C>[CH3:21][C:22]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:2](=[O:1])[C:3]([C:4]([OH:6])=[O:5])=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2285484,4-Dimethoxy-2-butanoneHCID 10942334Sodium MethoxideHCID 58816550Methyl 2-{[3-(trifluoromethyl)phenyl]carbamoyl}acetate

Product 1

HCID 117021046-Methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acidYield 73.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

Methyl 3-oxo-3-(3-(trifluoromethyl)phenylamino)propanoate (62.0 kg, 1 mol eq, limiting reagent) was charged followed by ethanol (310 L, 5 rel vol, 5.3 rel vol). 4,4-dimethoxybutan-2-one (37.6 kg, 1.2 mol eq) was charged followed by an ethanol line rinse (18.6 L, 0.3 rel vol) and the temperature adjusted to 50° C. Sodium methoxide (30% w/w in methanol) (141.0 kg, 3.3 mol eq) charged maintaining the temperature below 55° C. An ethanol line rinse (31.0 L, 0.5 rel vol) was applied. The reaction was stirred until complete as judged by HPLC. Water (105.4 L, 1.7 rel vol) and 29% aqueous sodium hydroxide solution (17.2 kg, 0.52 mol eq) were charged. The reaction was stirred for 60 minutes. Hydrochloric acid (30% w/w) was charged until pH 2 achieved and was then cooled. The product was isolated by filtration, washed five times with water (5×124 L, 5×2 rel vol) and dried under vacuum to constant weight yielding the title compound (50.9 kg, 171.4 mol, 73.5%).

Workup

  1. additionwas charged
  2. washrinse (18.6 L, 0.3 rel vol)
  3. customadjusted to 50° C
  4. temperaturemaintaining the temperature below 55° C
  5. washAn ethanol line rinse (31.0 L, 0.5 rel vol)
  6. stirringThe reaction was stirred for 60 minutes
  7. temperaturewas then cooled
  8. customThe product was isolated by filtration
  9. washwashed five times with water (5×124 L, 5×2 rel vol)
  10. customdried under vacuum to constant weight

Sources & evidence

ORD record
ord-a489726e694e485186f28c0e9d98524b
Source dataset
uspto-grants-2013_05
Patent number
US08436024B2

Reaction notes

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