Triethylamine → 1-(2-Deoxy-5-O-trityl-beta-D-threo-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

HRID 2181378Notes

Reaction equation

HRID 2181378 reaction equation
[C:1]([O:20][CH2:21][C@H:22]1[O:26][C@@H:25]([N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[CH2:24][C@@H:23]1[OH:36])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.S(Cl)(C)(=O)=O.[OH-].[Na+]>C1COCC1.C(O)C.O>[C:1]([O:20][CH2:21][C@H:22]1[O:26][C@@H:25]([N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[CH2:24][C@H:23]1[OH:36])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium Hydroxide2×HCID 31297Methanesulfonyl chlorideHCID 5141781-[2-Deoxy-5-O-(triphenylmethyl)pentofuranosyl]-5-methylpyrimidine-2,4(1H,3H)-dione

Product 1

HCID 117550831-(2-Deoxy-5-O-trityl-beta-D-threo-pentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 50-ml one-necked flask with lateral stopcock, 5′-O-tritylthymidine and triethylamine are placed in THF at t=0° C. under inert gas and stirring. Mesyl chloride is added dropwise from a syringe. The initially colorless solution becomes faintly yellow and cloudy. The reaction solution is allowed to warm up to room temperature within 30 minutes under stirring. Instead of the spot corresponding to starting material (Rf=0.29), a spot corresponding to the mesylated compound (Rf=0.45) is evident in TLC (V(MeOH):V(CH2Cl2)=1:19). At this point, 5 ml each of water, ethanol and 1 M sodium hydroxide solution are added to the reaction solution, which is stirred for 1 hour under reflux. In the TLC control test (V(MeOH):(VCH2Cl2)=1:19), exclusively the spot corresponding to the anhydro compound (Rf=0.15) is visible. Thereafter 3.4 ml of 10 M sodium hydroxide solution is added and the mixture stirred for 30 minutes under reflux. Two phases can form during this step. Instead of a spot corresponding to the anhydro compound (Rf=0.15), the product spot (Rf=0.33) is now evident on the TLC plate (V(MeOH):V(CH2Cl2)=1:19). The reaction solution is mixed with about 6 g of silica gel 60, and the solvent mixture is distilled off in the rotary evaporator. Subsequent column chromatography under flash conditions (silica gel 60; Ø=2.9 cm; h=32 cm; V(MeOH):V(CH2Cl2)=1:19+0.1% of triethylamine; 8.5 ml/min) yields the product, 1-(5-O-trityl-2-deoxy-β-D-lyxofuranosyl)thymine.

Workup

  1. stirringunder stirring
  2. stirringis stirred for 1 hour
  3. temperatureunder reflux
  4. stirringthe mixture stirred for 30 minutes
  5. temperatureunder reflux
  6. customTwo phases can form during this step
  7. additionThe reaction solution is mixed with about 6 g of silica gel 60
  8. distillationthe solvent mixture is distilled off in the rotary evaporator

Sources & evidence

ORD record
ord-29f59da9b23543f2a9e7e07855e33004
Source dataset
uspto-grants-2005_05
Patent number
US06891033B2

Reaction notes

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