3-Fluoroadamantane-1-carboxylic acid → 3-Fluoro-5-hydroxyadamantane-1-carboxylic acid

HRID 1106853Notes

Reaction equation

HRID 1106853 reaction equation
[OH-:1].[K+].[Mn]([O-])(=O)(=O)=O.[K+].[F:9][C:10]12[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:18][C:12]([C:20]([OH:22])=[O:21])([CH2:13]3)[CH2:11]1)[CH2:17]2>>[F:9][C:10]12[CH2:19][CH:14]3[CH2:15][C:16]([OH:1])([CH2:18][C:12]([C:20]([OH:22])=[O:21])([CH2:13]3)[CH2:11]1)[CH2:17]2

Participants

4

Reactant 3

HCID 134313-Fluoroadamantane-1-carboxylic acidHCID 14797Potassium HydroxideHCID 516875Potassium Permanganate2×

Product 1

HCID 187900243-Fluoro-5-hydroxyadamantane-1-carboxylic acidYield 42.7%

Conditions

Temperature
50 °C

Procedure

To an aqueous solution (400 ml) containing potassium hydroxide (13.0 g; 0.20 mol) was added 34.76 g (0.22 mol) of potassium permanganate and the solution was warmed on a steam bath (about 50° C). To this solution was added portion-wise 39.8 g (0.20 mol) of 3-fluoroadamantane-l-carboxylic acid. After the addition was complete, the reaction mixture was allowed to warm to a gentle reflux and stirred until all the potassium permanganate was consumed (about 1.5 hours). The reaction mixture was then cooled and acidified with 6N HCl. Sodium bisulfite was added to remove MnO2 and the white suspension was filtered and washed with water to yield recovered starting material (19.0 g). The aqueous filtrate was saturated with NaCl and extracted with 95:5 EtOAc:MeOH (4×350 ml). The organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 18.3 g (43%; 81% based on recovered 3-fluoroadamantan-1-carboxylic acid) of 3-fluoro-5-hydroxyadamantane-1-carboxylic acid. To an aqueous solution (250 ml) containing tetrabutylammonium hydrogen sulfate (42g, 0.124 mol) was added portion-wise sodium bicarbonate (41.0 g, 0.496 mol). This solution was allowed to stir for 20 minutes at which point 26.5 g (0.124 mol) of 3-fluoro-5-hydroxyadamantane-1-carboxylic acid was added portion-wise. The reaction mixture was allowed to stir for 30 minutes, was concentrated in vacuo to afford a viscous oil which was dissolved in acetone (300 ml) and mixed with methyl iodide (40 ml) and allowed to stir for 48 hours. The crude reaction mixture was filtered, concentrated in vacuo and triturated with Et2O to remove tetrabutylammonium iodide and the crude filtrate was concentrated in vacuo to afford 31 g of crude ester which was chromatographed on 800 g of silica gel using 2:1 hexane:ethyl acetate to afford 23.5 g (83%) of the title compound: mp 51.5-52.6°C.; 1H NMR (CDCl3) 1.60-1.70 (4H, m), 1.75-1.82 (4H, m), 1.88-1.92 (3H, M), 1.94-1.98 (2H, m), 2.42-2.50 (1H, m) 3.67 (3H, s). 13C NMR (CDCl3) 30.52 (10.33), 36.36, 40.35, 42.60 (20.38), 45.16, 45.42 (10.18), 49.44 (17.36), 51.94, 70.62 (12.53), 92.71 (186.33), 175.04; Anal. Calc'd for C12H17O3F: C, 63.14; H, 7.51; N, F, 8.32; Found: C, 63.25; H, 7.38; F, 8.52.

Workup

  1. additionAfter the addition
  2. temperatureto warm to
  3. temperaturea gentle reflux
  4. customwas consumed (about 1.5 hours)
  5. temperatureThe reaction mixture was then cooled
  6. additionSodium bisulfite was added
  7. customto remove MnO2
  8. filtrationthe white suspension was filtered
  9. washwashed with water
  10. customto yield
  11. customrecovered
  12. extractionextracted with 95:5 EtOAc
  13. dry with materialThe organic extracts were dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d9b7f410ace543cd9392d57ee44c482e
Source dataset
uspto-grants-2000_05
Patent number
US06057364

Reaction notes

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