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

HRID 1517466노트

반응식

HRID 1517466 반응식
[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

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 962Water용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-0208735b0b654677a29e58e37f5ac1c8
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232296B2

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