4-Toluenesulfonyl chloride → 1-(3,5-Di-O-benzyl-4-C-(p-toluenesulphonyloxymethyl)-2-O-p-toluenesulphony-beta-D-ribofuranosyl)uracil

HRID 2100284Notes

Reaction equation

HRID 2100284 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@:13]([CH2:23][OH:24])([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:25]2[CH:32]=[CH:31][C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:10]1[OH:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>ClCCl.CN(C1C=CN=CC=1)C>[CH2:1]([O:8][C@@H:9]1[C@@:13]([CH2:23][O:24][S:40]([C:37]2[CH:38]=[CH:39][C:34]([CH3:44])=[CH:35][CH:36]=2)(=[O:42])=[O:41])([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:25]2[CH:32]=[CH:31][C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:10]1[O:33][S:40]([C:37]1[CH:38]=[CH:39][C:34]([CH3:44])=[CH:35][CH:36]=1)(=[O:42])=[O:41])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 542980801(3,5-Di-O-benzyl-4-C-hydroxymethyl-beta-D-ribofuranosyl)uracil

Product 1

HCID 106051711-(3,5-Di-O-benzyl-4-C-(p-toluenesulphonyloxymethyl)-2-O-p-toluenesulphony-beta-D-ribofuranosyl)uracilYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 1-(3,5-di-O-benzyl-4-C-hydroxymethyl-β-D-ribofuranosyl)uracil 41 (3.55 g, 7.81 mmol) in dichloromethane (50 cm3) were added DMAP (3.82 g) and p-toluenesulphonyl chloride (4.47 g, 23.5 mmol) at room temperature. Stirring was continued for 2 h, and dichloromethane (100 cm3) was added. The reaction mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate (2×75 cm3) and dried (Na2SO4). The organic phase was evaporated under reduced pressure and the residue was purified by silica gel column chromatography using dichloromethane/methanol (99.5:0.5, v/v) as eluent to give nucleoside 75 (4.65 g, 78%) as a white solid material. δH (CDCl3) 8.49 (1H, br s, NH), 7.67 (1H, d, J 8.3, 6-H), 7.51-7.03 (18H, m, Bn, Ts), 6.0 (1H, d, J 7.6, 1′-H), 5.05 (1H, m, 2′-H), 4.91 (2H, m, 5-H, Bn), 4.56 (2H, m, Bn), 4.42 (1H, d, J 10.4, Bn), 4.31 (1H, d, J 4.9, 3′-H), 4.05 (2H, m, 1″-H), 3.75-3.64 (2H, m, 5′-H), 2.41 (3H, s, CH3), 2.34 (3H, 8, CH3). δC (CDCl3) 162.2 (C-4), 149.5 (C-2), 146.0, 145.3 (Ts), 139.0 (C-6), 136.7; 131.9, 130.0, 129.9, 128.9, 128.7, 128.5, 128.4, 128.3, 128.2, 128.0, 127.6 (Bn, Ts) 102.7 (C-5), 85.5 (1′-C), 84.4 (4′-C), 79.2, 78.3, 75.1, 74.3, 72.4, 69.1 (Bn, 3′-C, 2′-C, 5′-C, 1″-C), 21.7, 21.6 (Ts). FAB-MS m/z 763. Found: C, 61.2; H, 4.4; N, 3.3; C38H38N2O11S2 requires C, 59.8; H, 5.0; N, 3.6.

Workup

  1. washThe reaction mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate (2×75 cm3)
  2. dry with materialdried (Na2SO4)
  3. customThe organic phase was evaporated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3dabc46fa5454721925723fe0b7d75f8
Source dataset
uspto-grants-2009_08
Patent number
US07572582B2

Reaction notes

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