Lithium hydroxide, monohydrate → ({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid

HRID 337016

반응식

HRID 337016 반응식
C[O:2][C:3](=[O:34])[CH2:4][NH:5][C:6]([C:8]1[S:9][C:10]([C:16]2[CH2:20][C:19]([C:25]3[CH:30]=[C:29]([Cl:31])[C:28]([F:32])=[C:27]([Cl:33])[CH:26]=3)([C:21]([F:24])([F:23])[F:22])[O:18][N:17]=2)=[C:11]2[CH2:15][CH2:14][CH2:13][C:12]=12)=[O:7].O[Li].O>C1COCC1.O>[Cl:31][C:29]1[CH:30]=[C:25]([C:19]2([C:21]([F:22])([F:24])[F:23])[O:18][N:17]=[C:16]([C:10]3[S:9][C:8]([C:6]([NH:5][CH2:4][C:3]([OH:34])=[O:2])=[O:7])=[C:12]4[CH2:13][CH2:14][CH2:15][C:11]=34)[CH2:20]2)[CH:26]=[C:27]([Cl:33])[C:28]=1[F:32]

참가 물질

5

반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 86693751({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid methyl ester

생성물 1

HCID 86693752({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

Stir a mixture of ({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid methyl ester (11 g, 18.6 mmol) and LiOH—H2O (1.56 g, 37.2 mmol) in THF (100 mL) and water (50 mL) at room temperature for overnight. After being checked with TLC, the solvent is removed under vacuum, dilute the residue with water (50 mL). Acidify the aqueous mixture with 2M HCl to pH=3, and extract the resultant mixture with EtOAc (100 mL×3), the combined organic layer is washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum, the residue is purified by silica gel chromatograph (PE:EtOAc 1:1) to afford ({3-[5-(3,5-Dichloro-4-fluoro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carbonyl}-amino)-acetic acid as a white solid (10.2 g, 90.7% for two steps). MS (m/z): 525 (M+1).

후처리

  1. customthe solvent is removed under vacuum
  2. additiondilute the residue with water (50 mL)
  3. extractionextract the resultant mixture with EtOAc (100 mL×3)
  4. washthe combined organic layer is washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under vacuum
  7. customthe residue is purified by silica gel chromatograph (PE:EtOAc 1:1)

출처 및 근거

ORD 기록
ord-9832d1b89d2a44b790c3bd82977eaa63
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889710B2

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