N,N,N',N'-Tetramethylazodicarboxamide → Ethyl 2-(3-((5-(difluoromethyl)furan-2-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylate

HRID 2067696Notes

Reaction equation

HRID 2067696 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].[F:18][CH:19]([F:27])[C:20]1[O:24][C:23]([CH2:25]O)=[CH:22][CH:21]=1.C(P(CCCC)CCCC)CCC.N(C(N(C)C)=O)=NC(N(C)C)=O>O1CCCC1>[F:18][CH:19]([F:27])[C:20]1[O:24][C:23]([CH2:25][N:14]2[CH2:15][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:17])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 13831TributylphosphineHCID 20079677(5-(Difluoromethyl)furan-2-yl)methanolHCID 57919776Ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate

Product 1

HCID 58031437Ethyl 2-(3-((5-(difluoromethyl)furan-2-yl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylateYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate (0.35 g, 1.37 mmol) and (5-(difluoromethyl)furan-2-yl)methanol (0.20 g, 1.37 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise tributylphosphine (0.51 mL, 2.06 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 10 minutes and followed by the addition of 1,1′-azobis(N,N-dimethylformamide) (0.35 g, 2.06 mmol). The reaction mixture was stirred at ambient temperature for 18 hours, quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (4×20 mL). The organic solutions were combined, dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (1/4) to afford the title compound as a white solid in 53% yield (0.25 g): 1H NMR (300 MHz, CDCl3) δ 6.60-6.50 (m, 1H), 6.52 (t, JH-F=54.2 Hz, 1H), 6.37-6.29 (m, 1H), 4.45 (s, 2H), 4.21 (q, J=7.1 Hz, 2H), 4.09-3.98 (m, 2H), 3.60-3.49 (m, 2H), 2.54 (s, 3H), 1.27 (t, J=7.1 Hz, 3H); MS (ES+) m/z 386.3 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 18 hours
  2. customquenched with saturated aqueous ammonium chloride solution
  3. extractionextracted with ethyl acetate (4×20 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with ethyl acetate/hexane (1/4)

Sources & evidence

ORD record
ord-c4a9f277d7fa4ea8b3747b332941e903
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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