Diethyl Ether → Benzyloxymethyl-5'-O-tert-butyldiphenylsilylthymidine

HRID 2288264Notes

Reaction equation

HRID 2288264 reaction equation
[Si:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[CH2:22][C@@H:21]1[OH:34])([C:14]([CH3:17])([CH3:16])[CH3:15])([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.CCN(C(C)C)C(C)C.Cl[CH2:45][O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.CCOCC>C(Cl)Cl>[CH2:47]([O:46][CH2:45][C@@:23]1([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[O:24][C@H:20]([CH2:19][O:18][Si:1]([C:14]([CH3:15])([CH3:17])[CH3:16])([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@@H:21]([OH:34])[CH2:22]1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 137983Benzyl chloromethyl etherHCID 118128465'-O-tert-Butyldiphenylsilyl-thymidine

Product 1

HCID 131719888Benzyloxymethyl-5'-O-tert-butyldiphenylsilylthymidineYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2 (117.0 g, 243.8 mmol) and Hunig's base (diisopropylethylamine, 63.0 g, 487.5 mmol) in CH2Cl2 (400 mL) at 23° C. was added a solution of benzyl chloromethyl ether (40.7 g, 260.0 mmol) over a 15 min. period. The resultant mixture was maintained at 23° C. and stirred for 14 h. Ether (1 L) was added to the mixture and the ethereal solution was washed with 10% aqueous HCl (2×100 mL) and H2O (200 mL). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2 /AcOEt 40:1 then 10:1) to yield 128.9 g (88%) of 3 as a white solid. Rf (CH2Cl2 /AcOEt 10:1) 0.31. 1H-NMR (CDCl3): 1.10 (s, 9H, C-Me3), 1.65 (s, 3H, 5-Me), 2.16 (m, 1H, 2'-Hβ), 2.41 (m, 1H, 2'-Hβ), 2.53 (br s, 1H 3'-OH), 3.84 (d, 1H, J=8.8 Hz, 5'-CHH), 3.98 (d, 1H, J=8.8 Hz, 5'-CHH), 4.01 (s, 1H, 4'-H), 6.64 (br s, 1H, 3'-H), 4.70 (s, 2H, OCH2Ph), 5.50 (s, 2H, NCH2O), 6.41 (dd, 1H, J=8.0, 5.8 Hz, 1'-H), 7.20-7.50 (m, 13H, aromatic-H), 7.65-7.69 (m, 3H, 6-H and aromatic-H). 13C-NMR (CDCl3): 12.86 (-5-CH3) 19.45 (+, C-Me3), 27.09 (-, C-Me3), 41.16 (+, 2'-C), 64.25 (+, 5'-C), 70.70 (+, O--C--Ph), 71.97 (-, 4'-C), 72.29 (+, N--C--O), 85.51 (-, 3'-C), 87.20 (-, 1'-C), 110.47 (+, 5-C), 127.72, 128.08, 128.36 (-, aromatic-C), 130.25 (-, 6-C), 132.42, 133.00 (+, aromatic-C) 134.39, 135.37, 135.62 (-, aromatic-C), 137.95 (+, aromatic-C), 151.01 (+, 2-C), 163.68 (+, 4-C).

Workup

  1. washthe ethereal solution was washed with 10% aqueous HCl (2×100 mL) and H2O (200 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (CH2Cl2 /AcOEt 40:1

Sources & evidence

ORD record
ord-bf6a18538b5c4300935e6a3a86769db2
Source dataset
uspto-grants-2000_07
Patent number
US06087482

Reaction notes

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