Pyridine, hydrofluoride (1:1) → Benzyloxymethyl-3'-O-benzoylthymidine

HRID 975195Notes

Reaction equation

HRID 975195 reaction equation
[CH2:1]([O:8][CH2:9][C@@:10]1([N:43]2[CH:51]=[C:49]([CH3:50])[C:47](=[O:48])[NH:46][C:44]2=[O:45])[O:42][C@H:22]([CH2:23][O:24][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[C@@H:12]([O:13][C:14](=[O:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.F>C1COCC1.CCOC(C)=O>[CH2:1]([O:8][CH2:9][C@@:10]1([N:43]2[CH:51]=[C:49]([CH3:50])[C:47](=[O:48])[NH:46][C:44]2=[O:45])[O:42][C@H:22]([CH2:23][OH:24])[C@@H:12]([O:13][C:14](=[O:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 131719889Benzyloxymethyl-3'-O-benzoyl-5'-O-tert-butyldiphenylsilylthymidine

Product 1

HCID 86750437Benzyloxymethyl-3'-O-benzoylthymidineYield 97%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The silyl ether 4 (96.0 g, 136.4 mmol) in THF (600 mL) was treated with hydrogen fluoride-pyridine (70% HF in pyridine, 30 mL) at 0° C. for 4 h under a N2 atmosphere. The resultant mixture was diluted with AcOEt (600 mL) and washed with H2O (2×300 mL). The organic layer was dried (MgSO4) and concentrated at reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2 /AcOEt 10:1) to give 61.6 g (97%) of 5 as a white solid. Rf (CH2Cl2 /AcOEt 10:1) 0.29. 1H-NMR(CDCl3 +D2O): 1.95 (s, 3H, 5-Me), 2.53 (m, 2H, 2'-H), 4.00 (m, 2H, 5'-H), 4.25 (m, 1H, 4'-H), 4.71 (s, 2H, O--CH2 --Ph), 5.51 (s, 2H, N--CH2 --O), 5.60 (m, 1H 3'-H), 6.36 (dd, 1H, J=7.6, 6.6 Hz, 1'-H), 7.25-7.66 (m, 9H, 6 -H and aromatic-H), 8.05 (d, 2H, J=7.1 Hz, aromatic-H). 13C-NMR(CDCl3): 13.29 (-, 5-Me), 37.82 (+, 2'-C), 62.54 (+, 5'-C), 70.73 (+, O--C--Ph), 72.25 (+, N--C--O), 75.82 (-, 4'-C), 85.43 (-, 3'-C), 86.13 (-, 1'-C), 110.41 (+, 5-C), 127.65, 128.36, 128.59 (-, aromatic-C), 129.34 (+, aromatic-C), 129.69 (-, 6-C), 133.60, 135.40 (-, aromatic-C), 137.87 (+, aromatic-C), 151.18 (+, 2-C), 163.65 (+, 4C), 166.11 (+, benzoyl C=O).

Workup

  1. washwashed with H2O (2×300 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated at reduced pressure
  4. customThe residue was purified by silica gel column chromatography (CH2Cl2 /AcOEt 10:1)

Sources & evidence

ORD record
ord-49101824f0654086a88a8d3c80fb58f0
Source dataset
uspto-grants-1997_03
Patent number
US05608046

Reaction notes

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