Sodium bis(trimethylsilyl)amide → HCID 54201453, compound

HRID 248440Notes

Reaction equation

HRID 248440 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.[CH2:19]([C:23]1[NH:24][C:25]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])=[C:26]([Cl:28])[N:27]=1)[CH2:20][CH2:21][CH3:22].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.[Cl-].[Na+].O>[CH3:18][O:17][C:15]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:24]2[C:25]([CH2:29][O:30][Si:31]([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:32])[CH3:33])=[C:26]([Cl:28])[N:27]=[C:23]2[CH2:19][CH2:20][CH2:21][CH3:22])=[CH:4][CH:5]=1)=[O:16]

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 11012181Methyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 156656272-Butyl-5-chloro-4-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-1H-imidazole

Product 1

HCID 54201453HCID 54201453, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of methyl 4'-bromomethylbiphenyl-2-carboxylate (2.05 g) in dry THF (10 mL) was added dropwise to a solution of 2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazole (2.03 g) and NaN(TMS)2 (1.48 g) in dry THF (20 mL) at 0° C. and the reaction mixture was stirred at room temperature overnight. It was diluted with brine and the organic layer was collected, dried over MgSO4, and evaporated under reduced pressure. The residue was purified by flash chromatography (EtOAc, silica) to separate the two regioisomeric alkylation products. The major isomer, 4'-[[2-butyl-4 chloro-5-(t-butyldimethylsilyloxymethyl) 1H-imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]carboxylic acid methyl ester (1.4 g) was used in the next step and the regiochemistry of this alkylation product was proven by NOE experiments at the stage of the hydrazide.

Workup

  1. customthe organic layer was collected
  2. dry with materialdried over MgSO4
  3. customevaporated under reduced pressure
  4. customThe residue was purified by flash chromatography (EtOAc, silica)
  5. customto separate the two regioisomeric alkylation products

Sources & evidence

ORD record
ord-df944f84fd2f4efc90943651c5524b51
Source dataset
uspto-grants-1993_05
Patent number
US05210204

Reaction notes

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