Ethyl chloroformate → Ethyl 4-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-2-carboxylate

HRID 1875213Notes

Reaction equation

HRID 1875213 reaction equation
[Li]CCCC.[CH3:6][C:7]([Si:10]([CH3:27])([CH3:26])[O:11][CH2:12][C:13]1[N:14]=[CH:15][N:16]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:17]=1)([CH3:9])[CH3:8].Cl[C:29]([O:31][CH2:32][CH3:33])=[O:30]>C1COCC1>[CH3:9][C:7]([Si:10]([CH3:27])([CH3:26])[O:11][CH2:12][C:13]1[N:14]=[C:15]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:16]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:24])([CH3:23])[CH3:25])[CH:17]=1)([CH3:6])[CH3:8]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 220223854-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 70937136Ethyl 4-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-2-carboxylateYield 83.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

nBuLi (2.2 mL of a 1.9M solution in hexanes, 4.2 mmol) was added dropwise to a −78° C. solution of 4-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole (1.20 g, 3.5 mmol) in THF (10 mL). The reaction mixture was stirred at −60° C. for 2 h, cooled to −78° C. and ethyl chloroformate (0.70 mL, 7.3 mmol) was added dropwise. The solution was allowed to warm to RT, quenched by addition of sat'd NaHCO3 and extracted with CH2Cl2. The organic phase was dried (Na2SO4), filtered, and purified by silica gel chromatography (0-50% EtOAc/hex) to afford the title compound (1.21 g, 83%) as a light brown oil and as a mixture of the expected two isomers. Major isomer: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.05 (s, 1H), 5.90 (s, 2H), 4.75 (s, 2H), 4.34-4.43 (m, 2H) 3.48-3.58 (m, 2H) 1.40 (t, J=7.15 Hz, 3H), 0.91-0.89 (m, 2H), 0.87 (s, 9H), 0.06 (s, 6H), −0.06 (s, 9H).

Workup

  1. temperaturecooled to −78° C.
  2. temperatureto warm to RT
  3. customquenched by addition of sat'd NaHCO3
  4. extractionextracted with CH2Cl2
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. custompurified by silica gel chromatography (0-50% EtOAc/hex)

Sources & evidence

ORD record
ord-1b26e3c0567242249182815b71dafceb
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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