(3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-5-(fluoromethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole synthesis

7synthesis methods

Product Name:(3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-5-(fluoromethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole
CAS Number:196604-54-3
Molecular formula:C23H27FO5
Molecular Weight:402.46

153186-10-8 Synthesis

1,2-O-(1-methylethylidene)-4-C-[(phenylmethoxy)methyl]-3-O-(phenylmethyl)-L-Lyxofuranose

153186-10-8
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(3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-5-(fluoromethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole

196604-54-3
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Yield:196604-54-3 55%

Reaction Conditions:

Stage #1: ((3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanolwith pyridine;trifluoromethylsulfonic anhydride in dichloromethane at 0; for 0.75 h;
Stage #2: with tetrabutyl ammonium fluoride in tetrahydrofuran;acetonitrile at 50;

Steps:

148 3,5-Di-O-benzyl-4-C-fluoromethyl-1,2-O-isopropylidene-cL-D-ribofuranose:

To a stirred solution of 433 (7.87 g, 19.65 mmol) in CH2C12 (190 mL) was added successively pyridine (2.37 mL, 29.5 mmol) and trifluoromethanesulfonic anhydride (3.64 mL, 21.62 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 45 mm. and then TLC indicated completion of reaction to a single, faster moving compound. After which, the mixture waswahed with water and brine. The combined aqueous layers were back extracted with CH2C12. The combined organic phase was dried (Na2SO4), concentrated under reduced pressure to give a light brown solid.The solid obtained from previous step was dissolved in acetonitrile (100 ml). A 1M solution of tetrabutylammonium fluoride in THF (78 mL, 78.0 mmol) was added and thereaction mixture was stirred at 50 °C for overnight. Removal of the solvent under reduced pressure and silica gel chromatography of the dark oily residue [10-15% EtOAc in Hexanes] gave 434 (4.3 g, 55%) as a colorless oil. ‘H NMR (400 MHz, CDC13); 5 7.34-7.26 (m, 1OH), 5.77 (d, J 3.6 Hz, 1H), 4.87 (dd, J 10.0, 48.8 Hz, 1H), 4.73 (d, J 10 Hz, 1H), 4.63-4.47 (m, 5H), 4.26 (dd, J= 1.6, 4.8 Hz, 1H), 3.61 (dd, J 1.6, 10.4 Hz, 1H), 3.55 (dd, J 1.6,10.4 Hz, 1H), 1.63 (s, 3H), 1.35 (s, 3H). ‘9F NMR (400 MHz, CDC13); 5 -28.46 (t, J 48.8 Hz).

References:

WO2015/38596,2015,A1 Location in patent:Page/Page column 282; 283

63593-03-3 Synthesis