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

HRID 554910Notes

Reaction equation

HRID 554910 reaction equation
[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]

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e85f85b6aa9b4a7286d0edfa47ae60be
Source dataset
uspto-grants-2011_11
Patent number
US08049016B2

Reaction notes

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