Reaction #554619

Reaction equation

NaHCO3

N4-benzoyl-5′-O-tert-butyldimethylsilyl-2′-deoxycytidine

DMSO

acetic anhydride

→

N4-benzoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxycytidine

Yield 73.0%

N4-Benzoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxycytidine

Yield 73.0%

Solvents

acetic acid

EtOAc

Conditions

Workup

1. 1
   workup.WAITDuring this period of time
2. 2
   Extractionextracted with CH2Cl2 (3×100 mL)
3. 3
   ExtractionThe combined organic extract
4. 4
   Washwas then washed with saturated solution of NaHCO3
5. 5
   Dryingdried over Na2SO4
6. 6
   Concentrationconcentrated under vacuum
7. 7
   OtherThe product was then purified by silica gel column chromatography (EtOAc: hex/2:1 to 9:1)

Procedure

3.5 g N4-benzoyl-5′-O-tert-butyldimethylsilyl-2′-deoxycytidine (5c) (7.65 mmol) was dissolved in a mixture consisting of 14.7 mL DMSO, 6.7 mL acetic acid, and 21.59 mL acetic anhydride and stirred for 48 h at room temperature. During this period of time, a complete conversion to product was observed by TLC (Rf=0.4, EtOAc:hex/10:1). The mixture was then neutralized with a saturated NaHCO3 solution and extracted with CH2Cl2 (3×100 mL). The combined organic extract was then washed with saturated solution of NaHCO3 and dried over Na2SO4, and concentrated under vacuum. The product was then purified by silica gel column chromatography (EtOAc: hex/2:1 to 9:1) to obtain N4-benzoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxycytidine (6c) as white powder in 73% yield (2.9 g, Rf=0.6, EtOAc:hex/9:1). HR-MS: obs. m/z 506.2134, cald. for C24H36O5N3SiS [M+H]+. 506.2145. 1H-NMR (CDCl3): δH 8.43 (d, J=7.1 Hz, 1H), 7.93 (m, 2H), 7.64 (m, 1H), 7.54 (m, 3H), 6.30 (m, 1H), 4.62 & 4.70 (2Xd, J=11.59 Hz, 2H), 4.50 (m, 1H), 4.19 (m, 1H), 3.84 & 3.99 (2Xdd, J=11.59 & 2.79 Hz, 2H), 2.72 (m, 1H), 2.21 (m, 1H), 2.14 (s, 3H), 0.99 (s, 9H), and 0.16 (s, 6H) ppm.

Source