Sodium hydride → 4-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-piperidine-1-carboxylic acid benzyl ester

HRID 79733Notes

Reaction equation

HRID 79733 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:18][C:19]([CH:22]3[CH2:26][CH2:25][CH2:24][N:23]3[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[N:20][CH: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+].[CH3:36][Si:37]([CH2:40][CH2:41][O:42][CH2:43]Cl)([CH3:39])[CH3:38]>CN(C=O)C.[NH4+].[Cl-].CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]2[N:18]([CH2:43][O:42][CH2:41][CH2:40][Si:37]([CH3:39])([CH3:38])[CH3:36])[C:19]([CH:22]3[CH2:26][CH2:25][CH2:24][N:23]3[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[N:20][CH:21]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 666207084-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 666201004-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-piperidine-1-carboxylic acid benzyl esterYield 32.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

4-[2-(1-tert-Butoxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-piperidine-1-carboxylic acid benzyl ester (6.8 g, 14.9 mmol) in DMF (115 mL) was treated with NaH (60% dispersion in mineral oil, 655 mg, 16.4 mmol) in one portion. After 5 min, the mixture was treated with SEMCl (2.75 mL, 15.7 mmol) in 0.1 mL portions over 10 min. The reaction was stirred for 3 hours and diluted with saturated NH4Cl solution (50 mL) and EtOAc (100 mL). The organic layer was washed with H2O (3 50 mL) and brine (50 mL). The solution was dried over MgSO4 and subjected to a 120 g SiO2 COMBIFLASH column (0-100% EtOAc-hexanes followed by 0-20% MeOH-EtOAc gradient) to afford 4-[2-(1-tert-butoxycarbonyl-pyrrolidin-2-yl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-piperidine-1-carboxylic acid benzyl ester (2.8 g, 32%): MS (ESI) m/z 585 [M+H]+.

Workup

  1. washThe organic layer was washed with H2O (3 50 mL) and brine (50 mL)
  2. dry with materialThe solution was dried over MgSO4

Sources & evidence

ORD record
ord-6782e7f332c642668b65fd0ca7eec2ac
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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