Sodium hydride → (1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-methoxy-2,5-dioxabicyclo[2.2.1]heptane

HRID 1689660Notes

Reaction equation

HRID 1689660 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@:15]([CH2:25][O:26]S(C)(=O)=O)([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]1O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>CN(C=O)C>[CH2:1]([O:8][C@H:9]1[C@H:10]2[O:26][CH2:25][C@:15]1([CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[O:14][C@H:11]2[O:12][CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 20610801Methyl 3,5-di-O-benzyl-4-C-methanesulfonyloxymethyl-alpha-D-ribofuranoside

Product 1

HCID 56975532(1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-methoxy-2,5-dioxabicyclo[2.2.1]heptane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 201 (3.32 g, 7.34 mmol) in anhydrous DMF (25 mL) was stirred at 0° C. and a 60% oil dispersion of sodium hydride (700 mg, 16.9 mmol) was added. The mixture was stirred at room temperature for 90 min, quenched with water (300 mL) and extracted with diethyl ether (2×300 mL). The combined extract was washed with water (200 mL) and dried (MgSO4). The solvent was removed under reduced pressure and the residue was purified by chromatography over silica gel with dichloromethane as eluent to give the two products 202 and 203 as clear oils (1.571 g, 60% and 0.777 g, 30% respectively). (1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-methoxy-2,5-dioxabicyclo[2.2.1]heptane (202). 1H NMR (CDCl3): δ 7.36-7.26 (10H, m, Bn), 4.81 (1H, s, H-1), 4.65 (1H, d, J 11.9 Hz, Bn), 4.61 (2H, s, Bn), 4.56 (1H, d, J 11.9 Hz, Bn), 4.11 (1H, s, H-2), 4.09 (1H, s, H-3), 4.01 (1H, d, J 7.5 Hz, H-5′), 3.80-3.77 (3H, m, H-5′, H-5), 3.39 (3H, s, OCH3); 13C NMR (CDCl3): δ 138.05, 137.36, 128.47, 128.44, 127.88, 127.73, 127.63 (Bn), 104.97 (C-1), 85.13 (C-4), 79.16 (C-3), 77.18 (C-2), 73.64 (Bn), 72.26, 72.10 (Bn, C-5′), 66.50 (C-5), 55.34 (OCH3); MS FAB: 379 (M+Na, 28%). Found: C, 70.55; H, 6.97; C21H24O5 requires C, 70.77; H, 6.79%. (1S,3R,4R,7S)-7-Benzyloxy-1-benzyloxymethyl-3-methoxy-2,5-dioxabicyclo-[2.2.1]heptane (203). 11-1 NMR (CDCl3): δ 7.36-7.26 (10H, m, Bn), 5.00 (1H, s, H-1), 4.67-4.54 (4H, m, Bn), 4.18 (1H, s, H-2), 3.99 (1H, s, H-3), 3.99-3.90 (2H, m, H-5′), 3.75-3.68 (2H, m, H-5), 3.49 (3H, s, OCH3); 13C NMR (CDCl3): δ 137.83, 137.53, 128.51, 128.48, 127.96, 127.82, 127.71, 127.62 (Bn), 104.05 (C-1), 88.44 (C-4), 79.54 (C-3), 77.16 (C-2), 73.68 (Bn), 72.61 (C-5′), 72.24 (Bn), 65.73 (C-5), 56.20 (OCH3); MS FAB: 379 (M+Na, 100%).

Workup

  1. customquenched with water (300 mL)
  2. extractionextracted with diethyl ether (2×300 mL)
  3. extractionThe combined extract
  4. washwas washed with water (200 mL)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by chromatography over silica gel with dichloromethane as eluent

Sources & evidence

ORD record
ord-52d4aa08f1f74a54a7a8f1ff377fc66e
Source dataset
uspto-grants-2012_04
Patent number
US08153365B2

Reaction notes

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