Hydrochloric Acid → 1-((2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-3-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

HRID 1797361Notes

Reaction equation

HRID 1797361 reaction equation
C([O:4][CH2:5][C@:6]1([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:10][C@@H:9]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[C@H:8]([O:20]C(=O)C)[C@@H:7]1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=O)C.C[O-].[Na+].Cl>CO>[CH2:25]([O:24][C@@H:7]1[C@@:6]([CH2:5][OH:4])([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:10][C@@H:9]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[C@@H:8]1[OH:20])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 153742661-(4-C-(Acetoxymethyl)-2-O-acetyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)thymine

Product 1

HCID 110379851-((2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-3-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of nucleoside 34 (533 mg, 1.05 mmol) in methanol (5.5 cm3) was added sodium methoxide (287 mg, 5.25 mmol). The reaction mixture was stirred at room temperature for 10 min, then neutralised with dilute hydrochloric acid. The solvent was partly evaporated and extraction was performed with dichloromethane (2×20 cm3). The combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×20 cm3) and was dried (Na2SO4). The solvent was removed under reduced pressure to give 35 as a white solid material (476 mg, 97%). δH (CDCl3) 7.47 (1 H, d, J 1.0 6-H), 7.36-7.22 (10 H, m, Bn), 6.07 (1 H, d, J 3.8, 1′-H), 4.87 (1 H, d, J 11.7, Bn), 4.55 (1 H, d, J 11.7, Bn), 4.50-4.32 (4 H, m, Bn, 2′-H, 3′-H), 3.84-3.53 (4 H, m, 5′-Ha, 5′-Hb, 1″-Ha, 1″-Hb), 1.50 (3 H, d, J 1.1, CH3). δC (CDCl3) 164.3 (C-4), 151.3 (C-2), 137.6 (C-6), 136.4, 136.3, 128.8, 128.6, 128.4, 128.3, 127.9 (Bn), 111.1 (C-5), 91.1, 91.0, 88.1 (C-1′, C-3′, C-4′), 77.4 (C-2′), 74.8, 73.8, 71.4, 63.2 (Bn, C-5′, C-1″), 12.0 (CH3). FAB-MS m/z 491 [M+Na]+. Found: C, 63.4; H, 6.0; N, 5.5; C25H28N2O7, ¼ H2O requires C, 63.5; H, 6.1; N, 5.9%.

Workup

  1. customThe solvent was partly evaporated
  2. extractionextraction
  3. washThe combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×20 cm3)
  4. dry with materialwas dried (Na2SO4)
  5. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-fd0bdb94cbf5424eb75076885d8e9b10
Source dataset
uspto-grants-2006_04
Patent number
US07034133B2

Reaction notes

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