Methyl iodide → Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]-1-methyl-1H-benzo[d]imidazol-2-yl}piperidine-1-carboxylate

HRID 710117Notes

Reaction equation

HRID 710117 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:33]=[CH:32][C:15]2[NH:16][C:17]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[N:18][C:14]=2[CH:13]=1.[H-].[Na+].CI.[CH3:38]COC(C)=O.O>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:9])=[O:10])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:33]=[CH:32][C:15]2[N:16]([CH3:38])[C:17]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:21][CH2:20]3)=[N:18][C:14]=2[CH:13]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 22728543Water ethylacetateHCID 178451785HCID 178451785, compound

Product 1

HCID 71114581Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]-1-methyl-1H-benzo[d]imidazol-2-yl}piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-benzo[d]imidazol-2-yl}piperidine-1-carboxylate (85 mg, 0.17 mmol) dissolved in THF (15 ml) and cooled to 0° C. Sodium hydride (9 mg, 0.342 mmol) added to the above mixture and stirred at the same temperature for 30 mins. To this mixture methyl iodide (48 mg, 0.342 mmol) added at same temperature and stirred the reaction mixture at rt for 3 h. Reaction mixture diluted with ice and worked up (EtOAc/H2O). Crude was purified by column chromatography on 60-120 mesh silica gel using EtOAc:Petether (3:1) as eluent to afford the title compound (50 mg) as an orange solid. M.P.: 85-88° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 7.85-7.75 (m, 2H), 7.73-7.64 (m, 2H), 7.56-7.51 (m, 1H), 7.50-7.45 (m, 1H), 4.39-4.21 (m, 2H), 3.82 (s, 3H), 3.11 (s, 3H), 3.10-3.00 (m, 2H), 3.00-2.88 (m, 2H), 2.05-1.93 (m, 3H), 1.48 (s, 9H).

Workup

  1. stirringstirred the reaction mixture at rt for 3 h
  2. customReaction mixture
  3. additiondiluted with ice
  4. customCrude was purified by column chromatography on 60-120 mesh silica gel

Sources & evidence

ORD record
ord-44f72d6a54d74c3ba456d622c8321d21
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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