Sodium hydride → 2-[5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 417434Notes

Reaction equation

HRID 417434 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][N:27]=[C:26]([O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:25]=3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:40][Si:41]([CH3:48])([CH3:47])[CH2:42][CH2:43][O:44][CH2:45]Cl.[Cl-].[NH4+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[N:14]([CH2:45][O:44][CH2:43][CH2:42][Si:41]([CH3:48])([CH3:47])[CH3:40])[C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][N:27]=[C:26]([O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:25]=3)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 666202502-{5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666201842-[5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-{5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.530 g) in DMF (5.0 mL) at 0° C. was added 60% sodium hydride (0.047 g). After stirring for 5 minutes, 2-(trimethylsilyl)ethoxylmethyl chloride was added and reaction mixture stirred for 2 hours. Saturated ammonium chloride was added and mixture was extracted with ethyl acetate (2×). Organic layer was washed with 5% lithium chloride solution (2×), brine and dried (MgSO4). Concentrated and purified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexanes) to give 2-[5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.495 g). LCMS-ESI+: calc'd for C36H47N4O4Si: 627.87 (M+H+). Found: 627.1 (M+H+). A mixture of 2-[5-[4-(2-Benzyloxy-pyridin-4-yl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.495 g) and 10% Pd/C (0.023 g) in ethanol (5.5 mL) was stirred under hydrogen atmosphere for 1 hour. Reaction mixture was filtered through a pad of Celite, which was washed with methanol. The filtrate was concentrated and purifed by flash column chromatography (silica gel, 0 to 10% methanol/ethyl acetate) to give 2-[5-[4-(2-oxo-1,2-dihydro-pyridin-4-yl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.3027 g): LCMS-ESI+: calc'd for C29H41N4O4Si: 537.47 (M+H+). Found: 537.0 (M+H+).

Workup

  1. customreaction mixture
  2. stirringstirred for 2 hours
  3. extractionmixture was extracted with ethyl acetate (2×)
  4. washOrganic layer was washed with 5% lithium chloride solution (2×), brine
  5. dry with materialdried (MgSO4)
  6. concentrationConcentrated
  7. custompurified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cfd01095a61d400a8b25e46f9f02c92c
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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