Sodium Methoxide → 1-(2-Deoxy-4-thiopentofuranosyl)-4-hydroxy-5-methylpyrimidin-2(1H)-one

HRID 232533Notes

Reaction equation

HRID 232533 reaction equation
C1(C)C(C([O:9][C@@H:10]2[C@@H:14]([CH2:15][O:16]C(C3C(C)=CC=CC=3)=O)[S:13][C@@H:12]([N:26]3[CH:34]=[C:32]([CH3:33])[C:30](=[O:31])[NH:29][C:27]3=[O:28])[CH2:11]2)=O)=CC=CC=1.C[O-].[Na+]>CO>[C@@H:12]1([N:26]2[CH:34]=[C:32]([CH3:33])[C:30](=[O:31])[NH:29][C:27]2=[O:28])[S:13][C@H:14]([CH2:15][OH:16])[C@@H:10]([OH:9])[CH2:11]1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 69725700HCID 69725700, compound

Product 1

HCID 723711-(2-Deoxy-4-thiopentofuranosyl)-4-hydroxy-5-methylpyrimidin-2(1H)-oneYield 78.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 3',5'-di-O-toluoyl-4'-thiothymidine (formula β-17) (150 mg, 0.30 mmol) in anhydrous MeOH (30 mL) was stirred at room temperature with a freshly prepared solution of sodium methoxide (32.5 mg, 0.60 mmol) in MeOH (7.5 mL). A TLC aliquot at 3 hours showed complete consumption of starting material (TLC CHCl3 -MeOH 95:5). The solution was rendered neutral with Dowex 50W-X8 (H+) ion-exchange resin, the suspension was filtered, and the resin was washed with MeOH. The filtrates were combined and evaporated to dryness, and methyl p-toluate was removed at 50° C./0.01 torr. Crystallization of the residue from absolute EtOH gave pure 4'-thiothymidine (61 mg, 78%), mp 213°-215° C.; TLC 9:1 CHCl3 -MeOH, Rf =0.40; MS z/e 258 (M+1)+, UV λmax pH 1 272 (10.3), pH 7 272 (10.2), pH 13 271 (10.3 ); 1H NMR (Me2SO-d6, 300 MHz) δ1.80 (S, 3H, C-5, CH3), 2.10-2.24 (m, 2H, H-2'), 3.24-3.32 (m, 1H, H-4'), 3.50-3.66 (m, 2H, H-5'), 4.38 (br s, 1H, H-3'), 5.16 (br t, 1H, 5'-OH), 5.24 (d, 1H, 3'-OH, J=4 Hz), 6.30 (dd, 1, H-1', J=6.5 and 8 Hz), 7.32 (s, 1H, H-6), 11.32 (br s, 1H, H-3); 13C NMR (Me2SO-d6, 300 MHz) δ12.14 (C-5, CH3) 40.93 (C-1', JC,H =132.33 Hz), 59.01 (C-4', JC,H =143.3 Hz), 59.93 (C-1', JC,H =161.74), 63.51 (C-5'), 73.40 (C-3') 109.82 (C-5), 136.70 (C-6, JC,H =179 Hz), 150.59 (C-4) 163.37 (C-2) Anal Calcd. for C10H13N2O4S: C, 46.68; H, 5.09;N, 10.88; S, 12.46. Found: C, 46.59 H, 5.56; N, 10.74; S, 12.18.

Workup

  1. customconsumption of starting material (TLC CHCl3 -MeOH 95:5)
  2. filtrationthe suspension was filtered
  3. washthe resin was washed with MeOH
  4. customevaporated to dryness, and methyl p-toluate
  5. customwas removed at 50° C./0.01 torr
  6. customCrystallization of the residue from absolute EtOH

Sources & evidence

ORD record
ord-edec228c84f545f8b8f0133f0b33ba8f
Source dataset
uspto-grants-1997_01
Patent number
US05591722

Reaction notes

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