Reaction #1994277

Reaction equation

NaHCO3

Chlorotrimethylsilane

material ( 8 )

5′-O-(tert-Butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2′-deoxycytidine

Benzoyl chloride

→

solid ( 13 )

Yield 74.0%

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

Yield 74.0%

Solvents

pyridine

DCM

pyridine

Conditions

Workup

1. 1
   workup.STIRRINGstirred for one further hour
2. 2
   TemperatureThe reaction mixture was cooled to 0° C.
3. 3
   workup.DISTILLATIONdistilled water (50 ml)
4. 4
   workup.ADDITIONadded slowly to the solution
5. 5
   workup.STIRRINGstirred for 30 minutes
6. 6
   OtherPyridine and water were evaporated from mixture under high vacuum
7. 7
   Otherto yield a brown gel that
8. 8
   OtherThe organic phase was separated
9. 9
   Extractionthe aqueous phase extracted with a further (2×100 ml) of DCM
10. 10
    Dryingdried (MgSO4)
11. 11
    Filtrationfiltered
12. 12
    Otherthe volatiles evaporated under reduced pressure
13. 13
    OtherThe resulting brown oil was purified by flash chromatography on silica gel (DCM:MeOH 99:1 to 95:5)

Procedure

The starting material (8) (10 g, 20.43 mmol) was azeotroped in dry pyridine (2×100 ml) then dissolved in dry pyridine (160 ml) under N2 atmosphere. Chlorotrimethylsilane (10 ml, 79.07 mmol) added drop wise to the solution and stirred for 2 hours at room temperature. Benzoyl chloride (2.6 ml, 22.40 mmol) was then added to solution and stirred for one further hour. The reaction mixture was cooled to 0° C., distilled water (50 ml) added slowly to the solution and stirred for 30 minutes. Pyridine and water were evaporated from mixture under high vacuum to yield a brown gel that was portioned between 100 ml of sat. aq. NaHCO3 (100 ml) solution DCM. The organic phase was separated and the aqueous phase extracted with a further (2×100 ml) of DCM. The organic layers were combined, dried (MgSO4), filtered and the volatiles evaporated under reduced pressure. The resulting brown oil was purified by flash chromatography on silica gel (DCM:MeOH 99:1 to 95:5) to yield a light yellow crystalline solid (13) (8.92 g, 74%). 1H NMR (d6 DMSO): b 0.00 (s, 6H, CH3), 0.78 (s, 9H, tBu), 1.94 (m, 1H, H-2′), 2.27 (m, 1H, H-2′), 3.64 (d, 1H, J=11.6 Hz, H-5′), 3.75 (d, 1H, J=11.6 Hz, H-5′), 3.91 (m, 1H, H-4′), 4.09 (br m, 3H, CH2NH, H-3′), 5.24 (s, 1H, 3′-OH), 6.00 (m, 1H, H-1′), 7.39 (m, 2H, Ph), 7.52 (m, 2H, Ph), 7.86 (m, 1H, Ph), 8.0 (s, 1H, H-6), 9.79 (t, 1H, J=5.4 Hz, NHCH2), 12.67 (br s, 1H, NH). Mass (+ve electrospray) calcd for C27H33F3N4O6Si 594.67. Found 595.

Source