Sodium hydride → Benzyl 4-(1-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2284048Notes

Reaction equation

HRID 2284048 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.[H-].[Na+].[C:35]([O:39][C:40]([N:42]1[CH2:46][CH2:45][CH:44](OS(C)(=O)=O)[CH2:43]1)=[O:41])([CH3:38])([CH3:37])[CH3:36]>CN(C=O)C>[C:35]([O:39][C:40]([N:42]1[CH2:46][CH2:45][CH:44]([N:18]2[CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[C:24]([C:29]([F:32])([F:30])[F:31])[CH:23]=3)[N:21]=[C:17]2[CH:14]2[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])[CH2:16][CH2:15]2)[CH2:43]1)=[O:41])([CH3:38])([CH3:36])[CH3:37]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 4139999Tert-butyl 3-(methanesulfonyloxy)pyrrolidine-1-carboxylateHCID 178525121HCID 178525121, compound

Product 1

HCID 89442661Benzyl 4-(1-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylateYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[4-(4-Fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid benzyl ester (1000.00 mg; 2.24 mmol; 1.00 eq.) in DMF 8 ml added NaH (107.27 mg; 2.68 mmol; 1.20 eq.), stirred at RT for 20 mins, added 3-methanesulfonyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester (1186.02 mg; 4.47 mmol; 2.00 eq.), the reaction mixture was stirred 85° C. for 5 hr, lc-ms showed around 40% desired, continued stirring for over night, no big changed, purified the product by HPLC (basic) with 30-100% acetonitrile/water, collected title compound 220 mg, yield 16%.

Workup

  1. stirringthe reaction mixture was stirred 85° C. for 5 hr
  2. stirringcontinued stirring for over night
  3. customno big changed, purified the product by HPLC (basic) with 30-100% acetonitrile/water

Sources & evidence

ORD record
ord-9a6d18b508e945a59b2b7f0fd2720baa
Source dataset
uspto-grants-2015_09
Patent number
US09145392B2

Reaction notes

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