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

Temperature

-60 °C

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).

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)

ORD record

ord-1b26e3c0567242249182815b71dafceb

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304419B2