Adenosine, N,N-bis[(1,1-diMethylethoxy)carbonyl]-2',3'-O-(1-Methylethylidene)- synthesis

Yield: 89%

Reaction Conditions:

with dmap in tetrahydrofuran for 4 h;

Steps:

Preparation of CAS: 1152172-19-4
CAS: 139301-93-2 (12.5 g, 26.7 mmol) and DMAP (0.362 g, 2.97 mmol) were dissolved in THF (100 mL). Di-tert-butyl carbonate (20.6 g, 94.3 mmol) in THF (50 mL) was added dropwise. After 4 hours, the reaction mixture was diluted with water, extracted with EtOAc, and washed with brine and NaHCO3 (aq. sat.). The organic layer was dried (MgSO4), filtered and the filtrate was concentrated in vacuo to obtain CAS 1152172-19-4. The product was used in the next step without further purification.89% yield (16.2 g, 26,5 mmol), yellow oil. 1H NMR (400 MHz, Chloroform-d) d 8.85 (s, 1H), 8.14 (s, 1H), 5.96 (d, J=4.7 Hz, 1H), 5.39 (br d, J=10.9 Hz, 1H), 5.20-5.25 (m, 1H), 5.13 (dd, J=1.4, 6.0 Hz, 1H), 4.56 (d, J=1.5 Hz, 1H), 4.00 (d, J=12.8 Hz, 1H), 3.79-3.87 (m, 1H), 1.66 (s, 3H), 1.48 (s, 18H), 1.40 ppm (s, 3H).

References:

JANSSEN PHARMACEUTICA NV;VERHOEVEN, Jonas;BRAMBILLA, Marta;CHINTA, Nagaraju;HULLAERT, Jan, Julien, A;JOUFFROY, Lucile, Marguerite;MEERPOEL, Lieven;NEOUCHY, Zeïna;THURING, Johannes, Wilhelmus, John, F;VERNIEST, Guido, Alfons, F;WINNE, Johan, Maurits WO2020/249663, 2020, A1 Location in patent:Page/Page column 203