Water → 3'-Chloro-3-fluoro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-6-yl)-propyl]-biphenyl-4-carboxylic acid

HRID 2096835

반응식

HRID 2096835 반응식
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:35])[C:18]([OH:34])([C:23]3[CH:33]=[CH:32][C:26]4[N:27]([CH3:31])[C:28](=[O:30])[O:29][C:25]=4[CH:24]=3)[C:19]([F:22])([F:21])[F:20])=[C:13]([Cl:36])[CH:12]=2)=[CH:7][C:6]=1[F:37])=[O:4].[Li+].[OH-].O>C1COCC1>[Cl:36][C:13]1[CH:12]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:3]([OH:4])=[O:2])=[C:6]([F:37])[CH:7]=2)[CH:16]=[CH:15][C:14]=1[CH:17]([CH3:35])[C:18]([OH:34])([C:23]1[CH:33]=[CH:32][C:26]2[N:27]([CH3:31])[C:28](=[O:30])[O:29][C:25]=2[CH:24]=1)[C:19]([F:22])([F:20])[F:21]

참가 물질

5

반응물 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 666971423'-Chloro-3-fluoro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-6-yl)-propyl]-biphenyl-4-carboxylic acid methyl ester

생성물 1

HCID 666970833'-Chloro-3-fluoro-4'-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-6-yl)-propyl]-biphenyl-4-carboxylic acid수율 22.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

3′-Chloro-3-fluoro-4′-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-6-yl)-propyl]-biphenyl-4-carboxylic acid methyl ester (60 mg, obtained in Example 134, step 1) was dissolved in THF (4 mL) followed by the addition of aqueous LiOH solution (1.0M, 0.145 mL). The mixture was stirred over night at r.t. The reaction mixture was poured into water and extracted with ethyl acetate. The aqueous phase was acidified with 2 M aqueous HCl to pH 1 and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH=7:3 to 1:1) to give the title compound as a brown solid (13 mg, 22%). MS (neg. ion, m/e)=522.2 [(M−H)−].

후처리

  1. extractionextracted with ethyl acetate
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated
  6. customThe residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH=7:3 to 1:1)

출처 및 근거

ORD 기록
ord-dcf3f01ede7d47bea4bdd3723ee7821d
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450313B2

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