Proton sponge → HCID 69927702, compound

Temperature

0 °C

500 mg (1.51 mmol) of tert-butyl 1-((tert-butyldimethylsilyloxy)methyl)-3-hydroxycyclobutylcarbamate (prepared by reduction of ethyl-1[[tert-butyloxy)carbonyl]amino]-3-hydroxycyclobutane-1-carboxylate as described in J. Med. Chem., 1990 33(10) 2905-2915) and proton sponge (N,N,N′,N′ tetramethylnapthalene-1,8 diamine) (1.63 g, 6.04 mmol) were dissolved in DCM (18 mL), cooled down to 0° C., and 447 mg (3.02 mmol) of trimethyloxonium borontetrafluoride was added in one portion as a solid under vigorous stifling. The reaction mixture was stirred for 3 h and diluted with DCM (50 mL) and brine (20 mL), added under vigorous stifling. The organic phase was washed with sodium bicarbonate, brine, dried over sodium sulphate, evaporated and purified on short silica column (DCM as an eluent). The resulting product was dissolved in THF (5 mL), and a solution of tetrabutylammonium fluoride in THF (1M, 4.5 mL) was added, and the reaction was stirred at room temperature for 4.5 h. The reaction was monitored by TLC and once deemed to have reached completion, it was absorbed onto silica and purified on silica (EtOAc-hexane 1:1 to neat EtOAc) to give the title compound (251 mg, 72%). LC/MS 232 (M+1).

1. additionadded under vigorous stifling
2. washThe organic phase was washed with sodium bicarbonate, brine
3. dry with materialdried over sodium sulphate
4. customevaporated
5. custompurified on short silica column (DCM as an eluent)
6. dissolutionThe resulting product was dissolved in THF (5 mL)
7. additiona solution of tetrabutylammonium fluoride in THF (1M, 4.5 mL) was added
8. stirringthe reaction was stirred at room temperature for 4.5 h
9. customwas absorbed onto silica
10. custompurified on silica (EtOAc-hexane 1:1 to neat EtOAc)

ORD record

ord-78abca0f00984f468394b76ac342e85d

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859505B2