Hydrochloric Acid → 6-{3-Chloro-4-[2-(1,5-dimethyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-trifluoromethyl-nicotinic acid

HRID 1096023

反応式

HRID 1096023 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:25])[C:10]([C:16]1[CH:17]=[C:18]([CH3:24])[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].C([O:28][C:29](=[O:41])[C:30]1[CH:35]=[CH:34][C:33](Cl)=[N:32][C:31]=1[C:37]([F:40])([F:39])[F:38])C.[Li+].[OH-].Cl>CN(C)C(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[CH:9]([CH3:25])[C:10]([C:16]1[CH:17]=[C:18]([CH3:24])[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=1)([OH:15])[C:11]([F:13])([F:14])[F:12])[O:8][C:33]1[CH:34]=[CH:35][C:30]([C:29]([OH:41])=[O:28])=[C:31]([C:37]([F:38])([F:40])[F:39])[N:32]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 18374277Ethyl 6-chloro-2-(trifluoromethyl)nicotinateHCID 666993015-[2-(2-Chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1H-pyridin-2-one

生成物 1

HCID 723105706-{3-Chloro-4-[2-(1,5-dimethyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-2-trifluoromethyl-nicotinic acid

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

To a solution of 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1H-pyridin-2-one (Example 203, step 5, 60 mg) in N,N-dimethylacetamide (2 ml) were added potassium-tert.-butylate (21.5 mg) and 6-chloro-2-trifluoromethyl-nicotinic acid ethyl ester (81 mg). The mixture was stirred at room temperature for 1.5 h. A 0.2 M aqueous LiOH solution (4.79 ml) was added and the mixture was stirred at room temperature for 3 h and then cooled in an ice bath. The mixture was acidified with 1 M aqueous HCl and extracted with ethyl acetate. The organic phase was concentrated to dryness and the product was purified by chromatography ((SiO2, CH2Cl2/MeOH 1:0=>3:1). Off-white solid (22 mg). MS (m/e)=565.2 [M+H+].

後処理

  1. stirringthe mixture was stirred at room temperature for 3 h
  2. temperaturecooled in an ice bath
  3. extractionextracted with ethyl acetate
  4. concentrationThe organic phase was concentrated to dryness
  5. customthe product was purified by chromatography ((SiO2, CH2Cl2/MeOH 1:0=>3:1)

出典と根拠

ORDレコード
ord-670e93807dc941d7bed01a7d09cd9992
出典データセット
uspto-grants-2012_03
特許番号
US08138189B2

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