Pyridine → Benzyloxymethyl-3'-O-(phenoxythiocarbonyl)-5'-O-tert-butyldiphenylsilylthymidine

HRID 1489459Notes

Reaction equation

HRID 1489459 reaction equation
ON1C(=O)CCC1=O.N1C=CC=CC=1.[CH2:15]([O:22][CH2:23][C@@:24]1([N:49]2[CH:57]=[C:55]([CH3:56])[C:53](=[O:54])[NH:52][C:50]2=[O:51])[O:48][C@H:28]([CH2:29][O:30][Si:31]([C:44]([CH3:47])([CH3:46])[CH3:45])([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@H:26]([OH:27])[CH2:25]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH:58]1[CH:63]=[CH:62][C:61]([O:64][C:65](Cl)=[S:66])=[CH:60][CH:59]=1>C1(C)C=CC=CC=1>[CH2:15]([O:22][CH2:23][C@@:24]1([N:49]2[CH:57]=[C:55]([CH3:56])[C:53](=[O:54])[NH:52][C:50]2=[O:51])[O:48][C@H:28]([CH2:29][O:30][Si:31]([C:44]([CH3:47])([CH3:46])[CH3:45])([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C@@H:26]([O:27][C:65]([O:64][C:61]2[CH:62]=[CH:63][CH:58]=[CH:59][CH:60]=2)=[S:66])[CH2:25]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 70498Phenyl thioxochloroformateHCID 80170N-HydroxysuccinimideHCID 131719888Benzyloxymethyl-5'-O-tert-butyldiphenylsilylthymidine

Product 1

HCID 131720249Benzyloxymethyl-3'-O-(phenoxythiocarbonyl)-5'-O-tert-butyldiphenylsilylthymidineYield 75.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

N-hydroxysuccinimide (3.9 g, 34 mmol) and pyridine (24.3 mL, 300 mmol) were added to a solution of the alcohol 3 (90.0 g, 150 mmol) in 1 L of toluene. The mixture was warmed up to 80° C. and stirred for 10 min. Phenyl chlorothionoformate (30 g, 174 mmol) was added to the solution and the resultant reaction mixture was stirred at 80° C. for 8 h. The hot toluene solution was decanted from solids. The solids were rinsed with AcOEt (2×30 mL) and the combined toluene solution and AcOEt washes were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes/AcOEt 9:1 then 3:1) to give 83.0 g (75.2%) of the title compound, 17, as a light yellow foam. Rf (hexanes/AcOEt 9:1) 0.24. 13C-NMR (CDCl3): 12.97 (5-CH3), 19.49 (2'-C), 27.16 (Me3C), 38.32 (Me3C), 64.87 (O--C-Ph), 70.75 (N--C--O), 72.28 (5'-C), 84.21 (4'-C), 84.90 (3'-C), 85.39 (1'-C), 110.82 (5-C), 121.95, 126.94, 127.72, 128.27, 128.40, 129.81 (Ar--C), 130.35 (6-C), 131.93, 132.79, 133.76, 135.38, 135.76, 138.30 (Ar--C), 151.05 (2-C), 153.42 (Ar--C), 163.40 (4-C), 194.36 (thioformate-C).

Workup

  1. customthe resultant reaction mixture
  2. stirringwas stirred at 80° C. for 8 h
  3. customThe hot toluene solution was decanted from solids
  4. washThe solids were rinsed with AcOEt (2×30 mL)
  5. concentrationthe combined toluene solution and AcOEt washes were concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexanes/AcOEt 9:1

Sources & evidence

ORD record
ord-d63386d69e6b4deeba7181776c40f72f
Source dataset
uspto-grants-1997_10
Patent number
US05677437

Reaction notes

Loading…