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 1773841

反応式

HRID 1773841 の反応式
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]

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-ec02b81bfdf24eaa95a7d5fafcea8c15
出典データセット
uspto-grants-2016_02
特許番号
US09255111B2

関連ノート

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