Reacción #1994279

Ecuación de reacción

Cyclohexene

material ( 14 )

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

Sodium azide

→

desired product

Rendimiento 55.0%

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

Rendimiento 55.0%

Disolventes

DMF

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe mixture stirred for 1 h at 0° C
3. 3
   OtroVolatiles were removed by evaporation
4. 4
   Otroto yield a light brown solid that
5. 5
   workup.STIRRINGstirred for 2.5 h at room temperature
6. 6
   Lavadoeluted with EtOAc
7. 7
   Otrothe volatiles removed by high vacuum evaporation
8. 8
   OtroThe resulting brown gel was purified by flash chromatography (petroleum ether:EtOAc 4:1 to 2:1)

Procedimiento

The starting material (14) (1.65 g, 2.99 mmol) was dissolved in DCM (18 ml) and cooled to 0° C. Cyclohexene (1.5 ml, 14.95 mmol) and SO2Cl2 (0.72 ml, 8.97 mmol) were added and stirred 1 h in ice bath. TLC indicated starting material still to be present whereupon a further aliquot of SO2Cl2 (0.24 ml) was added and the mixture stirred for 1 h at 0° C. Volatiles were removed by evaporation to yield a light brown solid that was redissolved in 18 ml of dry DMF (18 ml) under N2. Sodium azide (0.97 g, 14.95 mmol) was then added to the solution and stirred for 2.5 h at room temperature. The reaction mixture was passed through a pad of silica and eluted with EtOAc and the volatiles removed by high vacuum evaporation. The resulting brown gel was purified by flash chromatography (petroleum ether:EtOAc 4:1 to 2:1) to yield the desired product as a white crystalline solid (15) (0.9 g, 55%). 1H NMR (d6 DMSO): δ 0.00 (s, 6H, CH3), 0.78 (s, 9H, tBu), 2.16 (m, 1H, H-2′), 2.22 (m, 1H, H-2′), 3.70 (d, 1H, J=11.5 Hz, H-5′), 3.75 (d, 1H, J=11.3 Hz, H-5′), 4.01 (m, 1H, H-4′), 4.10 (m, 1H, CH2NH), 4.23 (m, 1H, H-3′), 4.76 (s, 2H, CH2S), 5.99 (m, 1H, H-1′), 7.37 (m, 2H, Ph), 7.50 (m, 2H, Ph), 7.81 (d, 1H, J=7.4 Hz, Ph), 7.95 (s, 1H, H-6), 9.78 (br s, 1H, NHCH2), 12.64 (br s, 1H, NH). Mass (−ve electrospray) calcd for C28H34F3N7O6Si 649.71. Found 648.2

Fuente