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 2100267Notes

Reaction equation

HRID 2100267 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 (1 H, d, J 11.7, Bn), 4.50-4.32 (4 H, 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). 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, Cr5′, 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-898cf2d2775643ad9b68d90bcb2b5409
Source dataset
uspto-grants-2009_08
Patent number
US07572582B2

Reaction notes

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