Sodium hydride → Ethyl 3-methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiophene-2-carboxylate

HRID 2067461Notes

Reaction equation

HRID 2067461 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([N:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[S:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[H-].[Na+].[F:20][C:21]([F:31])([F:30])[C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][CH:23]=1>CN(C)C=O>[CH3:1][C:2]1[CH:6]=[C:5]([N:7]2[CH2:11][CH2:10][N:9]([CH2:26][C:25]3[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:30])[F:31])=[CH:29][CH:28]=3)[C:8]2=[O:12])[S:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 58031554Ethyl 3-methyl-5-(2-oxoimidazolidin-1-yl)thiophene-2-carboxylate

Product 1

HCID 58031427Ethyl 3-methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiophene-2-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of ethyl 3-methyl-5-(2-oxoimidazolidin-1-yl)thiophene-2-carboxylate (3.00 g, 11.8 mmol) in anhydrous N,N-dimethylformamide (20 mL) under nitrogen atmosphere was added in one portion sodium hydride (60% in mineral oil, 0.57 g, 14.15 mmol). The mixture was stirred for 1 hour, then 4-(trifluoromethyl)benzyl bromide (3.39 g, 14.16 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added. The resulting reaction mixture was stirred for 16 hours, then was partitioned between ethyl acetate (200 mL), water (100 mL) and brine (50 mL). The aqueous layer was extracted with ethyl acetate (200 mL) and the combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with 10% ethyl acetate in hexanes to afford the title compound as a cream solid in 89% yield (4.32 g): 1H NMR (300 MHz, CDCl3) δ 7.61 (d, J=8.1 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 6.17 (s, 1H), 4.53 (s, 2H), 4.28 (q, J=7.1 Hz, 2H), 3.86-3.79 (m, 2H), 3.50-3.43 (m, 2H), 2.50 (s, 3H), 1.34 (t, J=7.1 Hz, 3H); MS (ES+) m/z 413.3 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred for 16 hours
  3. customwas partitioned between ethyl acetate (200 mL), water (100 mL) and brine (50 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (200 mL)
  5. dry with materialthe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0fa0750e1bb1410ea1b27db9ea5f1c70
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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