Trifluoroacetic acid → (3R,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-one

HRID 505834Notes

Reaction equation

HRID 505834 reaction equation
[F:1][C:2](F)(F)[C:3]([OH:5])=[O:4].C([O:11][CH2:12][CH3:13])(=O)C.[CH3:14]CCCCCC.[O:21]1CCOC[CH2:22]1>O>[F:1][C@:2]1([CH3:14])[C@H:22]([OH:21])[C@@H:13]([CH2:12][OH:11])[O:5][C:3]1=[O:4]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 312751,4-DioxaneHCID 21899848Ethylacetate heptane

Product 1

HCID 56605413(3R,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-oneYield 83%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Deoxy-2-fluoro-3,4-O-isopropylidene-2-C-methyl-D-ribono-1,5-lactone (1.29 g, 6.317 mmol) was dissolved in anhydrous 1,4-dioxane (36.7 ml) under an atmosphere of argon. A pre-mixed solution of trifluoroacetic acid (146.8 ml) in water (36.7 ml) was added to the mixture slowly at room temperature. After 48 h, t.l.c. (ethyl acetate/heptane, 3:1) indicated conversion of the starting material (Rf 0.57) to faint products (Rf 0.47, 0.43, 0.38). The solvents were removed in vacuo at 35° C. and then coevaporated with toluene (5 ml×2). The crude off-white/brown residue (1.27 g) was purified by flash column chromatography (pre-adsorbed onto silica from ethyl acetate, eluted with ethyl acetate/heptane, 2:1) to give 2-deoxy-2-fluoro-2-C-methyl-D-ribono-1,4-lactone (862 mg, 83%, eluted second) as a white solid and 2-deoxy-2-fluoro-2-C-methyl-D-ribono-1,5-lactone (61 mg, 6%, eluted first) as a white solid, along with mixed fractions (115 mg, 11%).

Workup

  1. customThe solvents were removed in vacuo at 35° C.
  2. customThe crude off-white/brown residue (1.27 g) was purified by flash column chromatography (pre-adsorbed onto silica from ethyl acetate, eluted with ethyl acetate/heptane, 2:1)

Sources & evidence

ORD record
ord-9b87421ff59e48cca901bc7227015c77
Source dataset
uspto-grants-2010_08
Patent number
US07781576B2

Reaction notes

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