Reaction #1994278

Reaction equation

NaHCO3

Acetic acid

acetic anhydride

material ( 13 )

4-N-Benzoyl-5′-O-(tert-butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2′-deoxycytidine

DMSO

→

solid ( 14 )

Yield 50.0%

4-N-Benzoyl-5′-O-(tert-butyldimethylsilyl)-3′-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2′-deoxycytidine

Yield 50.0%

Conditions

Workup

1. 1
   ExtractionThe aqueous layer was extracted with EtOAc (3×150 ml)
2. 2
   Dryingdried (MgSO4)
3. 3
   Filtrationfiltered
4. 4
   Otherevaporated
5. 5
   Otherto yield an orange liquid that
6. 6
   Otherwas subsequently azeotroped with toluene (4×150 ml) until material
7. 7
   OtherCrude residue purified on silica gel (petroleum ether:EtOAc 3:1 to 2:1)

Procedure

The starting material (13) (2.85 g, 4.79 mmol) was dissolved in dry DMSO (40 ml) under N2 atmosphere. Acetic acid (2.7 ml, 47.9 mmol) and acetic anhydride (14.4 ml, 143.7 mmol) were added sequentially and slowly to the starting material, which was then stirred for 18 h at room temperature. Saturated NaHCO3 (150 ml) solution was carefully added to the reaction mixture. The aqueous layer was extracted with EtOAc (3×150 ml). The organic layers were combined, dried (MgSO4), filtered and evaporated to yield an orange liquid that was subsequently azeotroped with toluene (4×150 ml) until material solidified. Crude residue purified on silica gel (petroleum ether:EtOAc 3:1 to 2:1) to yield a yellow crystalline solid (14) (1.58 g, 50%). 1H NMR (d6 DMSO): δ 0.00 (s, 6H, CH3), 0.78 (s, 9H, tBu), 1.99 (s, 3H, CH3), 2.09 (m, 1H, H-2′), 2.28 (m, 1H, H-2′), 3.66 (d, 1H, J=11.5, 2.9 Hz, H-5′), 3.74 (dd, 1H, J=11.3, 2.9 Hz, H-5′), 3.99 (m, 1H, H-4′), 4.09 (m, 1H, CH2NH), 4.29 (m, 1H, H-3′), 4.61 (s, 2H, CH2S), 6.00 (m, 1H, H-1′), 7.37 (m, 2H, Ph), 7.50 (m, 2H, Ph), 7.80 (d, 1H, J=7.55 Hz, HAr), 7.97 (s, 1H, H-6), 9.79 (br t, 1H, NHCH2), 12.64 (br s, 1H, NH). Mass (−ve electrospray) calcd for C29H37F3N4O6SSi 654.79. Found 653.2.

Source