Methanol → 5'-O-(4,4'-Dimethoxytrityl)thymidine

HRID 378539

Reaction equation

HRID 378539 reaction equation
C(N(CC)CC)C.[C@@H:8]1([N:16]2[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[CH2:9]1.[CH3:25][O:26][C:27]1[CH:48]=[CH:47][C:30]([C:31](Cl)([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)=[CH:29][CH:28]=1.CO>C1COCC1>[CH3:39][O:38][C:35]1[CH:34]=[CH:33][C:32]([C:31]([O:14][CH2:13][C@H:12]2[O:15][C@@H:8]([N:16]3[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]3=[O:18])[CH2:9][C@@H:10]2[OH:11])([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:30]2[CH:47]=[CH:48][C:27]([O:26][CH3:25])=[CH:28][CH:29]=2)=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 5789ThymidineHCID 8471TriethylamineHCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)

Product 1

HCID 1624195'-O-(4,4'-Dimethoxytrityl)thymidineYield 85.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (10 ml) in 200 ml THF was injected into a solid mixture of 6.8 g (28.0 mmol) thymidine and 10.2 g (28.6 mmol) 4,4'-dimethyoxytrityl chloride under nitrogen with stirring. The solution was stirred at room temperature for 2 hours. After completion of the reaction, 10 ml methanol was added to consume the excess DMTrCl. The mixture was stirred for 5 minutes and the solvent removed by rotary evaporation. The residue was dissolved in 250 ml of ethyl acetate and the solution was washed with saturated NaHCO3 and dried over MgSO4. The solid was recrystallized from ethyl acetate/hexane to obtain 13.0 g 5'-protected thymidine 16 (85.6%).: m.p 124-126° C.; 1H NMR (200 MHz, CDCl3) δ8.97 (s, 1H, NH), 7.60 (m, 1H, H-6), 6.72-7.42 (m, 13H, Ph), 6.42 (m, 1H, H-1'), 4.56 (m, 1H, H-3'), 4.05 (m, 1H, H-4'), 3.78 (s, 6H, OMe2), 3.41 (m, 2H, H-5'), 2.62 (m, 1H, OH), 2.46 (m, 2H, H-2'), 1.46 (s, 3H, Me); 13C NMR (50 MHz, CDCl3) δ163.0 (C-4), 157.6, 149.8 (C-2), 143.5, 135.0 (C-6), 134.7, 134.6, 129.4, 127.4, 127.3, 126.5, 112.8, 110.9 (C-5), 86.7 (C-4'), 86.2, 84.7 (C-1'), 72.5 (C-3'), 63.8 (C-5'), 55.5 (OCH3), 41.3 (C-2'), 12.5 (CH3).

Workup

  1. stirringThe solution was stirred at room temperature for 2 hours
  2. additionwas added
  3. customto consume the excess DMTrCl
  4. stirringThe mixture was stirred for 5 minutes
  5. customthe solvent removed by rotary evaporation
  6. dissolutionThe residue was dissolved in 250 ml of ethyl acetate
  7. washthe solution was washed with saturated NaHCO3
  8. dry with materialdried over MgSO4
  9. customThe solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-c6faca36c8a0429dae4a1a5d38ad8a5f
Source dataset
uspto-grants-2000_02
Patent number
US06031092

Linked notes

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