Benzoyl chloride → Benzyloxymethyl-3'-O-benzoyl-5'-O-tert-butyldiphenylsilylthymidine

HRID 610463Notes

Reaction equation

HRID 610463 reaction equation
[CH2:1]([O:8][CH2:9][C@@:10]1([N:35]2[CH:43]=[C:41]([CH3:42])[C:39](=[O:40])[NH:38][C:36]2=[O:37])[O:34][C@H:14]([CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:12]([OH:13])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:44](Cl)([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:45]>C(Cl)Cl.CCN(CC)CC>[CH2:1]([O:8][CH2:9][C@@:10]1([N:35]2[CH:43]=[C:41]([CH3:42])[C:39](=[O:40])[NH:38][C:36]2=[O:37])[O:34][C@H:14]([CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:12]([O:13][C:44](=[O:45])[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 7412Benzoyl chlorideHCID 131719888Benzyloxymethyl-5'-O-tert-butyldiphenylsilylthymidine

Product 1

HCID 131719889Benzyloxymethyl-3'-O-benzoyl-5'-O-tert-butyldiphenylsilylthymidineYield 87%

Reagents, catalysts & solvents 1

HCID 21882572Triethylamine methylene chlorideSolvent

Procedure

A stirred solution of 3 (128.0 g, 213.3 mmol) in a 4:1 mixture of CH2Cl2 /Et3N (500 mL) was treated with (48.4 g, 40 mL, 344.6 mmol) of BzCl at 23° C. for 8 h. The resultant precipitate was removed by filtration. The filtrate was concentrated under reduced pressure to leave the crude product as a brownish syrup. Purification of the syrup by silica gel column chromatography (hexanes/AcOEt 10:1 then 1:1) gave 130.7 g (87%) of 4 as a white solid. Rf (Hexanes/AcOEt 1:1) 0.82 1H-NMR (CDCl3): 1.40 (s, 9H, C-Me3), 1.60 (s, 3H, 5-Me), 2.37 (ddd, 1H, J=13.8, 9.3, 7.2 Hz, 2'-Hβ), 2.62 (dd, 1H, J=13.8, 4.3 Hz, 2'-Hβ), 4.09 (m, 2H, 5'-H), 4.26 (m, 1H, 4'-H), 4.74 (s, 2H, O--CH2 -Ph), 5.54 (s, 2H, N--CH2 --O), 5.71 (d, 1H, J=7.2 Hz, 3'-H), 6.57 (dd, 1H, J=9.3, 4.3 Hz, 1'-H), 7.24-7.74 (m, 13H, aromatic-H), 8.05-8.15 (m, 3H, 6-H and aromatic-H). 13C-NMR(CDCl3): 12.82 (-, 5-Me), 19.54 (+, C-Me3), 27.16 (C-Me3), 38.28 (+, 2'-C), 64.41 (+, 5'-C), 70.80 (+, O--C-Ph), 72.29 (+, N--C--O), 75.60 (-, 4'-C), 85.28 (-, 1'-C and 3'-C), 110.95 (+, 5-C), 127.72, 128.23, 128.37, 128.50, 128.63 (-, aromatic-C), 129.43 (+, aromatic-C), 129.84, 130.22 (-, aromatic-C), 132.14, 133.07 (+, aromatic-C), 133.60 (-, 6-C), 133.94, 135.32, 135.65 (-, aromatic-C), 138.15 (+, aromatic-C), 151.19 (+, 2-C), 163.50 (+, 4-C), 166.11 (+, benzoyl C=O).

Workup

  1. customThe resultant precipitate was removed by filtration
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customto leave the crude product as a brownish syrup
  4. customPurification of the syrup by silica gel column chromatography (hexanes/AcOEt 10:1

Sources & evidence

ORD record
ord-802fbaa3af804396abc8766e29f1dda9
Source dataset
uspto-grants-1999_12
Patent number
US05998603

Reaction notes

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