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

HRID 417643

Reaction equation

HRID 417643 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:28][Si:29]([CH2:32][CH2:33][O:34][CH2:35]Cl)([CH3:31])[CH3:30]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[C:14]1[N:18]([CH2:35][O:34][CH2:33][CH2:32][Si:29]([CH3:31])([CH3:30])[CH3:28])[CH:17]=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=2)[N:15]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 666203882-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666211532-[4-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg) was dissolved in DMF (8 mL), and NaH (54 mg) was added. The mixture was stirred over 10 min. and SEM-Cl was added slowly, and then stirred for 2 hours. The mixture was quenched with 3 mL of sat. NH4Cl and was taken up in ethyl acetate (100 mL). The organic phase was washed with saturated sodium bicarbonate (1×100 mL) and dried over sodium sulfate. After the solvent was removed, the resulting oil was subjected to silica gel chromatography using effluent of 20-50% ethyl acetate and hexanes. The fractions containing product were combined and the solvent was removed under reduced pressure to provide 2-[4-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (648 mg, 98%) as an off-white solid.

Workup

  1. stirringstirred for 2 hours
  2. customThe mixture was quenched with 3 mL of sat. NH4Cl
  3. washThe organic phase was washed with saturated sodium bicarbonate (1×100 mL)
  4. dry with materialdried over sodium sulfate
  5. customAfter the solvent was removed
  6. additionThe fractions containing product
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-a5418df416054979ad878bfb18e03fd8
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Linked notes

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