Hydrochloric Acid → 2-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-pyrimidine-5-carboxylic acid

HRID 1095940ノート

反応式

HRID 1095940 の反応式
C[O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:32])[C:19]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=3)([OH:24])[C:20]([F:23])([F:22])[F:21])=[C:14]([Cl:33])[CH:13]=2)=[N:9][CH:10]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1.CO>[Cl:33][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[CH:18]([CH3:32])[C:19]([C:25]1[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[CH:26]=1)([OH:24])[C:20]([F:23])([F:21])[F:22])[O:11][C:8]1[N:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:10][N:9]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 595086402-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-pyrimidine-5-carboxylic acid methyl ester

生成物 1

HCID 595087562-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-pyrimidine-5-carboxylic acid収率 8.4%

試薬・触媒・溶媒 1

HCID 21899815MeOH tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

2-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenoxy}-pyrimidine-5-carboxylic acid methyl ester (27 mg) was dissolved in THF/methanol=5/1 (2.5 mL). The reaction mixture was cooled to 0° C. and aqueous LiOH solution (1.0 M, 0.092 mL) was added. The mixture was stirred at 0° C. for 1 hour. The reaction mixture was poured into ice/water and acidified with 1M aqueous HCl to pH 1. The aqueous phase was then extracted two times with ethyl acetate and the organic layers were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, ethyl acetate:heptane=50:50 to 100:0) to give the title compound as a colorless amorphous foam (2.2 mg, 8.4%). MS (neg. ion, m/e)=486.4 [(M−H)−].

後処理

  1. extractionThe aqueous phase was then extracted two times with ethyl acetate
  2. washthe organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customThe residue was purified by flash chromatography (silica gel, ethyl acetate:heptane=50:50 to 100:0)

出典と根拠

ORDレコード
ord-c878d0cb61774f19b182a1d828859223
出典データセット
uspto-grants-2012_03
特許番号
US08138189B2

反応ノート

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