4-Toluenesulfonyl chloride → HCID 10548431, compound

HRID 726423Notes

Reaction equation

HRID 726423 reaction equation
[C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10]O)[O:8][C@@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2].[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=O)=O)=[CH:23][CH:22]=1.C(=O)([O-])O.[Na+].C(N(CC)CC)C.C1(C)C=CC(S)=CC=1>N1C=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][S:27][C:24]2[CH:25]=[CH:26][C:21]([CH3:31])=[CH:22][CH:23]=2)[O:8][C@@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2]

Participants

7

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 78114-MethylbenzenethiolHCID 8471TriethylamineHCID 464365HCID 464365, compoundHCID 516892Sodium Bicarbonate

Product 1

HCID 10548431HCID 10548431, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 3'-O-acetylthymidine 26 (0.511 g, 1.8 mmol) and toluene-4-sulfonyl chloride (0.514 g, 2.7 mmol) in dry pyridine (3 cm3) was stirred at room temperature. After 16 h, saturated aqueous sodium hydrogen carbonate (2 cm3) was added and, after a further 10 min, the products were partitioned between chloroform (50 cm3) and saturated aqueous sodium hydrogen carbonate (50 cm3). The dried (MgSO4) organic layer was concentrated under reduced pressure. The residue was fractionated by short column chromatography on silica gel: the appropriate fractions, eluted with chloroform-methanol (99:1 v/v), were combined and evaporated under reduced pressure. The residue was dissolved in acetonitrile (2.5 cm3) at room temperature and triethylamine (0.90 cm3, 6.5 mmol) and toluene-4-thiol (0.805 g, 6.5 mmol) were added to the stirred solution which was kept under an atmosphere of argon. After 60 h, the products were concentrated under reduced pressure and the residue was fractionated by short column chromatography on silica gel: the appropriate fractions, eluted with chloroform-methanol (99:1 v/v) were combined and evaporated under reduced pressure to give 3'-O-acetyl-5'-S-(4-methylphenyl)-5'-thiothymidine 31 as a colourless glass (0.60 g, 85% based on 3'-O-acetylthymidine) (Found: M+ =390.1249. 12C191H2214N216 O532S requires: 390.1249); Rt 12.05 min (programme 1); δH [(CD3)2SO] 1.76 (3 H, d, JO.9), 2.05 (3 H, s), 2.25 (1 H, m), 2.26 (3 H, s), 2.49 (1 H, m), 3.32 (2 H, m), 4.02 (1 H, m), 5.18 (1 H, m), 6.13 (1 H, dd, J 6.0, 8.6), 7.14 (2 H, d, J7.9), 7.29 (2 H, d, J 8.2), 7.51 (I H, m), 11.38 (1 H, br s); δC [(CD3)2 SO] 12.1, 20.5, 20.8, 35.2, 35.4, 75.7, 81.9, 83.9, 110.0, 129.1, 129.7, 131.6, 135.7, 136.0, 150.5, 163.6, 169.9.

Workup

  1. customthe products were partitioned between chloroform (50 cm3) and saturated aqueous sodium hydrogen carbonate (50 cm3)
  2. dry with materialThe dried (MgSO4) organic layer
  3. concentrationwas concentrated under reduced pressure
  4. washthe appropriate fractions, eluted with chloroform-methanol (99:1 v/v)
  5. customevaporated under reduced pressure
  6. dissolutionThe residue was dissolved in acetonitrile (2.5 cm3) at room temperature
  7. waitAfter 60 h
  8. concentrationthe products were concentrated under reduced pressure
  9. washthe appropriate fractions, eluted with chloroform-methanol (99:1 v/v)
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-b543706cc90f404ea2b7cdcb3d9b8b07
Source dataset
uspto-grants-1998_01
Patent number
US05708161

Reaction notes

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