Cesium carbonate → (S)-ethyl 2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate

HRID 1882356Notes

Reaction equation

HRID 1882356 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:16][C@H:15]([CH3:17])[NH:14][C:13]2=[O:18])[S:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].C(=O)([O-])[O-].[Cs+].[Cs+].[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1>CC(=O)CC>[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][N:14]2[C@@H:15]([CH3:17])[CH2:16][N:12]([C:4]3[S:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]([CH3:1])[N:3]=3)[C:13]2=[O:18])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 680214-Fluorobenzyl bromideHCID 57919870(S)-ethyl 4-methyl-2-(4-methyl-2-oxoimidazolidin-1-yl)thiazole-5-carboxylate

Product 1

HCID 57919865(S)-ethyl 2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylateYield 87.3%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

To a solution of (S)-ethyl 4-methyl-2-(4-methyl-2-oxoimidazolidin-1-yl)thiazole-5-carboxylate (0.45 g, 1.67 mmol) in 2-butanone (20.0 mL) was added cesium carbonate (1.09 g, 3.34 mmol) and 4-fluorobenzyl bromide (0.40 g, 2.09 mmol). The reaction mixture was refluxed for 16 h, filtered and washed with acetone (150 mL). The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluted with 2-5% methanol in dichloromethane to afford the title compound as a colorless solid (0.55 g, 87%): 1H NMR (300 MHz, CDCl3) δ 7.40-7.35 (m, 2H), 7.21-7.15 (m, 2H), 4.60 (d, J=15.6 Hz, 1H), 4.31 (d, J=15.6 Hz, 1H), 4.26-4.17 (m, 3H), 3.79-3.72 (m, 1H), 3.57 (dd, J=10.3, 6.7 Hz, 1H), 2.52 (s, 3H), 1.27 (t, J=7.1 Hz, 3H), 1.22 (d, J=6.2 Hz, 3H); MS (ES+) m/z 377.9 (M+1).

Workup

  1. temperatureThe reaction mixture was refluxed for 16 h
  2. filtrationfiltered
  3. washwashed with acetone (150 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by column chromatography
  6. washeluted with 2-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-39d841dced1a4173aa1cf12159b814c4
Source dataset
uspto-grants-2012_11
Patent number
US08318949B2

Reaction notes

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