Pyridine → 5'-O-(4,4'-dimethoxytrityl)-2'-O-(2-cyanoethoxymethyl)uridine

HRID 1694673

Reaction equation

HRID 1694673 reaction equation
[C:1]([CH2:3][CH2:4][O:5][CH2:6][O:7][C@@H:8]1[C@H:12]([OH:13])[C@@H:11]([CH2:14][OH:15])[O:10][C@H:9]1[N:16]1[CH:23]=[CH:22][C:20](=[O:21])[NH:19][C:17]1=[O:18])#[N:2].N1C=CC=CC=1.[CH3:30][O:31][C:32]1[CH:53]=[CH:52][C:35]([C:36](Cl)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)=[CH:34][CH:33]=1>CO>[CH3:44][O:43][C:40]1[CH:39]=[CH:38][C:37]([C:36]([O:15][CH2:14][C@H:11]2[O:10][C@@H:9]([N:16]3[CH:23]=[CH:22][C:20](=[O:21])[NH:19][C:17]3=[O:18])[C@H:8]([O:7][CH2:6][O:5][CH2:4][CH2:3][C:1]#[N:2])[C@@H:12]2[OH:13])([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:35]2[CH:52]=[CH:53][C:32]([O:31][CH3:30])=[CH:33][CH:34]=2)=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 672789412'-O-(2-Cyanoethoxymethyl)uridine

Product 1

HCID 672792965'-O-(4,4'-dimethoxytrityl)-2'-O-(2-cyanoethoxymethyl)uridineYield 98%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2′-O-(2-Cyanoethoxymethyl)uridine (14 g, 43 mmol) was subjected to azeotropic distillation with pyridine, and then was dried with a vacuum pump for 30 minutes. The residue was dissolved in 300 mL of THF, and 68 g of pyridine (856 mmol), and 20 g of molecular sieve 4 A was added under an argon atmosphere, and the mixture was stirred for 10 minutes. To the solution was added 19.6 g of 4,4′-dimethoxytritylchloride (57.8 mmol) by 3 portions every 1 hour, and the mixture was further stirred for 1 hour. After 10 mL of methanol was added and the reaction solution was stirred for 2 minutes, the reaction solution was filtrated with a celite, and was washed with ethyl acetate. After concentrating the filtrate, the residue was dissolved in ethyl acetate, and was washed with a saturated aqueous sodium bicarbonate solution. After the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, the solvent was distilled off. The obtained residue was purified by silica gel chromatography to obtain the objective compound (26.5 g, yield 98%).

Workup

  1. customwas dried with a vacuum pump for 30 minutes
  2. dissolutionThe residue was dissolved in 300 mL of THF
  3. stirringthe mixture was further stirred for 1 hour
  4. stirringthe reaction solution was stirred for 2 minutes
  5. filtrationthe reaction solution was filtrated with a celite
  6. washwas washed with ethyl acetate
  7. concentrationAfter concentrating the filtrate
  8. dissolutionthe residue was dissolved in ethyl acetate
  9. washwas washed with a saturated aqueous sodium bicarbonate solution
  10. washAfter the organic layer was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. distillationthe solvent was distilled off
  13. customThe obtained residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-8b15a528422e42f18dc837496157d8f1
Source dataset
uspto-grants-2012_04
Patent number
US08158775B2

Linked notes

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