Tetrahydrofuran → HCID 23211168, compound

Temperature

-78 °C

Combine 1-((2-trimethylsilyl)ethoxymethyl)-1 H-benzimidazole (91.2 g, 367 mmol) and tetrahydrofuran (500 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of n-butyl]ithium (146 mL, 2.5 M in hexane, 367 mmol) at such a rate that the temperature of the reaction mixture remains at about −70° C. After the addition of n-butyllithium is complete allow to stir for 30 minutes at −78° C. Add a solution of 1-(t-butoxycarbonyl)-piperidine-4-(N-methyl-O-methyl)-hydroxamic acid (99.9 g, 367 mmol) in tetrahydrofuran (100 mL). Warm to ambient temperature. After 18 hours, add dropwise a saturated aqueous ammonium chloride solution (100 mL). Add water (300 mL) and extract with diethyl ether. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 10% ethyl acetone/hexane to give a residue. Recrystallize the residue from methanol/water to give (1-(t-butoxycarbonyl)-4-(1-((2-trimethylsilyl)ethoxymethyl)-1 H-benzoimidazole-2-carbonyl)-piperidine.

1. customremains at about −70° C
2. temperatureWarm to ambient temperature
3. waitAfter 18 hours
4. extractionAdd water (300 mL) and extract with diethyl ether
5. dry with materialDry the organic layer over MgSO4
6. filtrationfilter
7. customevaporate in vacuo
8. customto obtain a residue

ORD record

ord-3061e9c44e324be3b10dfa38a93df349

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06329392B1