Dimethyl Sulfoxide → N4-Benzoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxycytidine

HRID 1914430Notes

Reaction equation

HRID 1914430 reaction equation
[C:1]([NH:9][C:10]1[CH:30]=[CH:29][N:13]([C@@H:14]2[O:28][C@H:18]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@@H:16]([OH:17])[CH2:15]2)[C:12](=[O:31])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32][S:33]([CH3:35])=O.C(OC(=O)C)(=O)C.C([O-])(O)=O.[Na+]>CCOC(C)=O.C(O)(=O)C>[C:1]([NH:9][C:10]1[CH:30]=[CH:29][N:13]([C@@H:14]2[O:28][C@H:18]([CH2:19][O:20][Si:21]([C:24]([CH3:25])([CH3:26])[CH3:27])([CH3:23])[CH3:22])[C@@H:16]([O:17][CH2:32][S:33][CH3:35])[CH2:15]2)[C:12](=[O:31])[N:11]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 14018201N4-Benzoyl-5'-O-tert-butyldimethylsilyl-2'-deoxycytidine

Product 1

HCID 86649154N4-Benzoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxycytidineYield 73%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

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 (2×d, J=11.59 Hz, 2H), 4.50 (m, 1H), 4.19 (m, 1H), 3.84 & 3.99 (2×dd, 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.

Workup

  1. waitDuring this period of time
  2. extractionextracted with CH2Cl2 (3×100 mL)
  3. extractionThe combined organic extract
  4. washwas then washed with saturated solution of NaHCO3
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customThe product was then purified by silica gel column chromatography (EtOAc: hex/2:1 to 9:1)

Sources & evidence

ORD record
ord-b9b4013106c04bc5bdc913412c76fbb7
Source dataset
uspto-grants-2013_12
Patent number
US08612161B2

Reaction notes

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