Dimethyl Sulfoxide → Benzyl 4-(1-((1,3-dioxolan-2-yl)methyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2283948Notes

Reaction equation

HRID 2283948 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:18][CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:44][CH:45]1[O:49][CH2:48][CH2:47][O:46]1.CS(C)=O>C1COCC1.O>[O:46]1[CH2:47][CH2:48][O:49][CH:45]1[CH2:44][N:18]1[CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([C:29]([F:32])([F:30])[F:31])[CH:23]=2)[N:21]=[C:17]1[CH:14]1[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 780681,3-Dioxolane, 2-(bromomethyl)-HCID 2724254Sodium bis(trimethylsilyl)amideHCID 178525121HCID 178525121, compound

Product 1

HCID 89442873Benzyl 4-(1-((1,3-dioxolan-2-yl)methyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylateYield 76.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The solution of 4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester (1100.00 mg; 2.46 mmol; 1.00 eq.) in 2.0 ml of THF was cooled to −20° C., NaHMDS (541.00 mg; 2.95 mmol; 1.20 eq.) was added dropwise and the resulting mixture was stirred at RT for 30 mins. 2-Bromomethyl-[1,3]dioxolane (0.76 ml; 7.38 mmol; 3.00 eq.) was added and stirred at RT for 5 min. DMSO (10 ml) was added and the mixture was placed in microwave at 100° C. for 2 hr. The reaction mixture was cooled and diluted with water and extracted with EA. The organic layer was washed with brine, separated, dried and concentrated. The residue was subjected to snap column (100 g), eluted with 20%-80% EA in hexane to give the title compound (1000 mg, yield 76.2%).

Workup

  1. stirringstirred at RT for 5 min
  2. waitthe mixture was placed in microwave at 100° C. for 2 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with EA
  5. washThe organic layer was washed with brine
  6. customseparated
  7. customdried
  8. concentrationconcentrated
  9. washeluted with 20%-80% EA in hexane

Sources & evidence

ORD record
ord-6611739ee25a4b01a388c71d5e372826
Source dataset
uspto-grants-2015_09
Patent number
US09145392B2

Reaction notes

Loading…