Water → Tert-butyl (2S)-2-{(3-fluoro-4-methylphenyl)[(1H-imidazol-1-yl carbonothioyl)oxy]methyl}pyrrolidine-1-carboxylate

HRID 1920779Notes

Reaction equation

HRID 1920779 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]([OH:22])[C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[CH:6][C:7]=1[CH3:8].[C:23](N1C=CN=C1)([N:25]1[CH:29]=[CH:28][N:27]=[CH:26]1)=[S:24].O>CN(C)C1C=CN=CC=1.O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([O:22][C:23]([N:25]2[CH:29]=[CH:28][N:27]=[CH:26]2)=[S:24])[C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

6

Reactant 3

HCID 962WaterHCID 802641,1'-ThiocarbonyldiimidazoleHCID 58580880Tert-butyl (2S)-2-[(3-fluoro-4-methylphenyl)(hydroxy)methyl]pyrrolidine-1-carboxylate

Product 1

HCID 58580778Tert-butyl (2S)-2-{(3-fluoro-4-methylphenyl)[(1H-imidazol-1-yl carbonothioyl)oxy]methyl}pyrrolidine-1-carboxylateYield 47%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl (2S)-2-[(3-fluoro-4-methylphenyl)(hydroxy)methyl]pyrrolidine-1-carboxylate (1.30 g, 4.19 mmol), which had been obtained in Example 1 (1b), 1,1′-thiocarbonyldiimidazole (1.12 g, 6.28 mmol), and 4-(dimethylamino)pyridine (0.05 g, 0.42 mmol) were dissolved in tetrahydrofuran (8.4 mL) and stirred with heating under reflux for 16 hours. The reaction solution was cooled to room temperature. Water (20 mL) was added to the reaction solution, which was then extracted with ethyl acetate (20 mL×3). After that, the organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1) to give the title compound as a yellow wax like substance (0.83 g, yield 47%).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 16 hours
  3. extractionwas then extracted with ethyl acetate (20 mL×3)
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-4c672e5d764a46f2901bee01f593ca36
Source dataset
uspto-grants-2012_05
Patent number
US08173631B2

Reaction notes

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