Hydrochloric Acid → 2-(3-((2,2-Difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid

HRID 554910노트

반응식

HRID 554910 반응식
[F:1][C:2]1([F:23])[CH2:4][CH:3]1[CH2:5][N:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]([C:17]([O:19]CC)=[O:18])=[C:14]([CH3:16])[N:15]=2)[C:7]1=[O:22].O.[OH-].[Li+].Cl>O1CCCC1.O>[F:23][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]([C:17]([OH:19])=[O:18])=[C:14]([CH3:16])[N:15]=2)[C:7]1=[O:22]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 57919981Ethyl 2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate

생성물 1

HCID 579198122-(3-((2,2-Difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid수율 68.9%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of ethyl 2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate (0.77 g, 2.24 mmol) in tetrahydrofuran (40.0 mL) was added lithium hydroxide monohydrate (0.27 g, 11.2 mmol) in water (2.0 mL). The reaction mixture was heated at reflux for 16 h, cooled to an ambient temperature, then acidified with a solution of hydrochloric acid (3.0 N, 10.0 mL). The solvent was removed in vacuo to dryness and the precipitate was filtered, dried to afford the title compound as a colourless solid (0.49 g, 68%): mp 210-215° C.; 1H NMR (300 MHz, DMSO-d6) δ 12.79 (br, 1H), 3.99 (t, J=9.0 Hz, 2H), 3.64-3.48 (m, 3H), 3.19-3.12 (m, 1H), 2.46 (s, 3H), 2.02-1.88 (m, 1H), 1.67-1.55 (m, 1H), 1.37-1.26 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 164.0, 159.8, 156.0, 155.2, 115.2, 114.9 (t), 42.4, 42.1, 41.1 (d), 20.3 (t, 2JC-F=43 Hz), 17.4, 14.9 (t, 2JC-F=43 Hz); MS (ES+) m/z 318.0 (M+1).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. customThe solvent was removed in vacuo to dryness
  4. filtrationthe precipitate was filtered
  5. customdried

출처 및 근거

ORD 기록
ord-e85f85b6aa9b4a7286d0edfa47ae60be
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08049016B2

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