Potassium Carbonate → Ethyl 2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate

HRID 1882373Notes

Reaction equation

[CH3:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:16][CH2:15][NH:14][C:13]2=[O:17])[S:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:25][CH:26]1[CH2:28][C:27]1([F:30])[F:29]>O1CCOCC1>[F:29][C:27]1([F:30])[CH2:28][CH:26]1[CH2:25][N:14]1[CH2:15][CH2:16][N:12]([C:4]2[S:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]([CH3:1])[N:3]=2)[C:13]1=[O:17]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate (1.19 g, 4.68 mmol) in anhydrous dioxane (50.0 mL) was added potassium carbonate (1.29 g, 9.36 mmol) and bromomethyl-2,2-difluorocyclopropane (1.00 g, 5.85 mmol). The reaction mixture was heated at 80° C. for 16 h, filtered and the solid was washed with ethyl acetate (100 mL). The filtrate was concentrated in vacuo and the residue was recrystallized from ethyl acetate in hexane to afford the title compound as a yellow solid (0.87 g, 54%): mp 146-148° C.; 1H NMR (300 MHz, CDCl3) δ 4.18 (q, J=7.1 Hz, 2H), 3.99 (t, J=8.4 Hz, 2H), 3.65-3.44 (m, 3H), 3.20-3.12 (m, 1H), 2.48 (s, 3H), 2.02-1.88 (m, 1H), 1.68-1.55 (m, 1H), 1.38-1.28 (m, 1H), 1.23 (t, J=7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 162.5, 160.1, 156.8, 155.2, 114.9 (t), 113.8, 60.8, 42.4, 42.1, 41.1 (d), 20.3 (t, 2JC-F=43 Hz), 17.5, 14.9 (t, 2JC-F=43 Hz), 14.6; MS (ES+) m/z 399.0 (M+1).

Workup

filtrationfiltered
washthe solid was washed with ethyl acetate (100 mL)
concentrationThe filtrate was concentrated in vacuo
customthe residue was recrystallized from ethyl acetate in hexane

Sources & evidence

ORD record: ord-441d536e094a4269b4ff8c5e24c3c6f6
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318949B2

Reaction notes

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