Dichloromethane → 3-Fluoroadamantane-1-carboxylic acid

HRID 1106852Notes

Reaction equation

HRID 1106852 reaction equation
C(N(S(F)(F)[F:7])CC)C.ClCCl.O[C:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][C:16]([C:24]([O:26]C)=[O:25])([CH2:17]3)[CH2:15]1)[CH2:21]2.[OH-].[Na+]>O.O1CCCC1.CO>[F:7][C:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][C:16]([C:24]([OH:26])=[O:25])([CH2:17]3)[CH2:15]1)[CH2:21]2

Participants

8

Reactant 4

HCID 6344Dichloromethane2×HCID 14798Sodium HydroxideHCID 123472(Diethylamino)sulfur trifluorideHCID 144304Methyl 3-hydroxyadamantane-1-carboxylate

Product 1

HCID 134313-Fluoroadamantane-1-carboxylic acidYield 95%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Under a N2 atmosphere was added 26.17 ml (0.20 ml) of diethylaminosulfur trifluoride (DAST) to 24 ml. of dry dichloromethane which was cooled to -78° C. To this solution was added drop-wise a dichloromethane solution (10 ml) of methyl 3-hydroxyadamantane-1-carboxylate (42.0 g, 0.20 mol). The suspension was allowed to warm to ambient temperature and stirred for 1 hour. To the resultant solution was added water (500 ml). The organic layer was separated, washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford 41.6 g (98%) of crude product, mp <34° C, which slowly crystallized. 1H NMR (CDCl3) 1.70-1.80 (m-6H), 2.20-2.35(m-3H), 2.50-2.60 (m-6H), 7.00-7.70 (m-5H) 13C NMR (CDCl3) 30.84 (10.11), 34.79 (0.91), 37.56, 41.81 (17.73), 43.70 (20.15), 44.86 (10.16), 51.86, 92.13 (184.14). Under a N2 atmosphere was added to crude ester (41.6 g, 0.196 mol), 100 ml of methanol, 75 ml of tetrahydrofuran (THF), 50 ml of water followed by 16.0 g (0.40 mol) of NaOH pellets. The solution was allowed to stir overnight. The organic solvents were removed under reduced pressure, water (200 ml) was added and the solution was acidified to a pH of 1.0 with 6N HCl. The resultant solids were filtered, washed with water and air dried to afford 37.0 g (95%) of 3-fluoroadamantane-1-carboxylic acid (mp 154-156° C). An analytical sample of the title compound was obtained following an EtOAc/hexane recrystallization. Crystals from the recrystallization were suitable for X-ray analysis. Anal. Calc'd for C11H15O2F: C, 66.65; H, 7.63; F, 9.58; Found: C, 66.44; H, 7.72; F, 9.22.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford 41.6 g (98%) of crude product, mp <34° C, which
  7. customslowly crystallized
  8. stirringto stir overnight
  9. customThe organic solvents were removed under reduced pressure, water (200 ml)
  10. additionwas added
  11. filtrationThe resultant solids were filtered
  12. washwashed with water and air
  13. customdried

Sources & evidence

ORD record
ord-73725599b359433dafefc10983d0ba11
Source dataset
uspto-grants-2000_05
Patent number
US06057364

Reaction notes

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