Potassium Carbonate → (R)-ethyl 2-(4-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate

HRID 2067459Notes

Reaction equation

HRID 2067459 reaction equation
O[CH2:2][C@H:3]([NH:11][C:12](=[O:25])[NH:13][C:14]1[S:15][C:16]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:17]([CH3:19])[N:18]=1)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[CH2:4]([C@@H:3]1[CH2:2][N:13]([C:14]2[S:15][C:16]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:17]([CH3:19])[N:18]=2)[C:12](=[O:25])[NH:11]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 73213189(R)-ethyl 2-(3-(1-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate

Product 1

HCID 73213190(R)-ethyl 2-(4-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-ethyl 2-(3-(1-hydroxy-3-phenylpropan-2-yl)ureido)-4-methylthiazole-5-carboxylate (3.20 g, 8.80 mmol) and N,N-diisopropylethylamine (2.70 mL, 115.50 mmol) in tetrahydrofuran (50 mL) was added methanesulfonyl chloride (0.82 mL, 10.50 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 2 hours. To this reaction mixture was added potassium carbonate (1.38 g, 10.00 mmol), and heated to reflux for 17 hours. The solvent was removed in vacuo, the residue was dissolved in ethyl acetate (300 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography to afford the title compound in 47% yield (1.43 g): mp 102-103° C.; 1H NMR (300 MHz, acetone-d6) δ 9.38 (s, 1H), 7.37-7.23 (m, 5H), 4.60-4.17 (m, 5H), 3.07-2.95 (m, 2H), 2.44 (s, 3H) 1.26 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, acetone-d6) δ 174.9, 162.1, 161.7, 157.1, 136.9, 129.2, 128.7, 126.8, 113.0, 70.4, 60.1, 56.4, 40.3, 16.6, 13.7; MS (ES+) m/z 346.4 (M+1).

Workup

  1. temperatureheated
  2. temperatureto reflux for 17 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (300 mL)
  5. washwashed with water and brine
  6. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-48d10d845f9249269178eb88d791dd8f
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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