Acetic Anhydride → Methyl 2-O-acetyl-3,5-di-O-benzyl-4-C-methanesulfonyloxymethyl-D-ribofuranoside

HRID 1689662Notes

Reaction equation

HRID 1689662 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@:15]([CH2:25][O:26][S:27]([CH3:30])(=[O:29])=[O:28])([CH2:16][O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:14][C@H:11]([O:12][CH3:13])[C@@H:10]1[OH:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32](OC(=O)C)(=[O:34])[CH3:33]>N1C=CC=CC=1>[C:32]([O:31][C@@H:10]1[C@H:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C@@:15]([CH2:25][O:26][S:27]([CH3:30])(=[O:29])=[O:28])([CH2:16][O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[O:14][CH:11]1[O:12][CH3:13])(=[O:34])[CH3:33]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 20610801Methyl 3,5-di-O-benzyl-4-C-methanesulfonyloxymethyl-alpha-D-ribofuranoside

Product 1

HCID 11145450Methyl 2-O-acetyl-3,5-di-O-benzyl-4-C-methanesulfonyloxymethyl-D-ribofuranosideYield 100%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred solution of 201 (687 mg, 1.52 mmol) in anhydrous pyridine (4 mL) at 0° C. was added dropwise acetic anhydride (0.43 mL, 4.56 mmol). The reaction mixture was stirred for 2 days at room temperature, quenched with saturated aqueous sodium hydrogen carbonate (75 mL) and extracted with dichloromethane (150+75 mL). The combined extract was dried (MgSO4), the solvent was removed by distillation under reduced pressure and the residue was purified by chromatography over silica gel with dichloromethane as eluent to give the product 209 as a clear oil (β:α˜3:1, 750 mg, 100%); MS FAB: 463 (M-OCH3, 100%), 517 (M+Na, 28%); Found: C, 58.53; H, 6.16; C24H30O9S requires C, 58.29; H, 6.11%. Methyl 2-O-acetyl-3,5-di-O-benzyl-4-C-methanesulfonyloxymethyl-β-D-ribofuranoside (209β). 1H NMR (CDCl3): δ 7.36-7.18 (10H, m, Bn), 5.27 (1H, d, J 4.9 Hz, H-2), 4.88 (1H, s, H-1), 4.55-4.44 (6H, m, H-5′, Bn), 4.35 (1H, d, J 5.0 Hz, H-3), 3.73 (1H, d, J 9.2 Hz, H-5), 3.38 (1H, d, J 9.3 Hz, H-5), 3.30 (3H, s, OCH3), 2.95 (3H, s, SO2CH3), 2.11 (3H, s, OCCH3); 13C NMR (CDCl3): δ 169.91 (C═O), 137.83, 137.28, 128.49, 128.44, 127.99, 127.87, 127.77 (Bn), 105.40 (C-1), 82.65, 81.05, 74.55, 73.62, 73.56, 71.86, 70.22 (C-2, C-3, C-4, C-5, C-5′, Bn), 55.03 (OCH3), 37.14 (SO2CH3), 20.73 (OCCH3). Methyl 2-O-acetyl-3,5-di-O-benzyl-4-C-methanesulfonyloxymethyl-α-D-ribofuranoside (209α). 1H NMR (CDCl3): δ 7.36-7.18 (10H, m, Bn), 5.09 (1H, d, J 4.5 Hz, H-1), 4.95 (1H, dd, J 4.5, 6.8 Hz, H-2), 4.65-4.44 (6H, m, H-5′, Bn), 4.27 (1H, d, J 6.6 Hz, H-3), 3.49 (1H, d, J 9.9 Hz, H-5), 3.46 (3H, s, OCH3), 3.36 (1H, d, J 9.9 Hz, H-5), 2.92 (3H, s, SO2CH3), 2.14 (3H, s, OCCH3); 13C NMR (CDCl3): δ 170.41 (C═O), 137.59, 137.28, 128.56, 128.51, 128.49, 128.44, 127.98, 127.88 (Bn), 102.35 (C-1), 84.25, 77.53, 74.66, 73.67, 72.12, 70.39, 70.28 (C-2, C-3, C-4, C-5, C-5′, Bn), 56.07 (OCH3), 36.94 (SO2CH3), 20.63 (OCCH3).

Workup

  1. customquenched with saturated aqueous sodium hydrogen carbonate (75 mL)
  2. extractionextracted with dichloromethane (150+75 mL)
  3. extractionThe combined extract
  4. dry with materialwas dried (MgSO4)
  5. customthe solvent was removed by distillation under reduced pressure
  6. customthe residue was purified by chromatography over silica gel with dichloromethane as eluent

Sources & evidence

ORD record
ord-31c2a44b652543afabc169984d8c7fd7
Source dataset
uspto-grants-2012_04
Patent number
US08153365B2

Reaction notes

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