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 1689639Notes

Reaction equation

HRID 1689639 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 (553 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 (1H, d, J 1.0 6-H), 7.36-7.22 (10H, m, Bn), 6.07 (1H, d, J 3.8, 1′-H), 4.87 (1H, d, J 11.7, Bn), 4.55 (1H, d, J 11.7, Bn), 4.50-4.32 (4H, m, Bn, 2′-H, 3′-H), 3.84-3.53 (4H, m, 5′-Ha, 5′-Hb, 1″-Ha, 1″-Hb), 1.50 (3H, d, J 1.1, CH3). (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; C25H28N2O7,¼H2O 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-e5435be0f0524577a1e18d54fa4a327c
Source dataset
uspto-grants-2012_04
Patent number
US08153365B2

Reaction notes

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