Potassium Hydroxide → 4-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid

HRID 2280824Notes

Reaction equation

HRID 2280824 reaction equation
[C:1]12([C:13]([O:15]C)=[O:14])[CH2:8][CH2:7][C:4]([C:9]([O:11][CH3:12])=[O:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[OH-].[K+]>CO.O>[CH3:12][O:11][C:9]([C:4]12[CH2:7][CH2:8][C:1]([C:13]([OH:15])=[O:14])([CH2:6][CH2:5]1)[CH2:2][CH2:3]2)=[O:10]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 2802857dimethyl bicyclo[2.2.2]octane-1,4-dicarboxylate

Product 1

HCID 110420624-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acidYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

A solution of dimethyl bicyclo[2.2.2]octane-1,4-dicarboxylate (58.0 g, 0.25 mol) in methanol (600 mL) was heated to reflux and then a solution of potassium hydroxide (9.8 g, 0.175 mol) in methanol (100 mL) and water (12 mL) was added over 30 min. The reaction mixture was refluxed for 24 h and concentrated. The residue was diluted with water and extracted with ethyl acetate (200 mL×2) to recover some starting material (22.0 g). The resulting aqueous layer was acidified to pH=3 by addition of hydrochloric acid and extracted with ethyl acetate (300 mL×3). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the titled product (30.0 g, 0.14 mol, yield 55%). 1H NMR (400 MHz, CDCl3) δ ppm 3.65 (s, 3H), 1.81 (s. 12H); MS (ESI) m/z=211.3 [M+H]−.

Workup

  1. temperatureto reflux
  2. temperatureThe reaction mixture was refluxed for 24 h
  3. concentrationconcentrated
  4. additionThe residue was diluted with water
  5. extractionextracted with ethyl acetate (200 mL×2)
  6. customto recover some starting material (22.0 g)
  7. additionThe resulting aqueous layer was acidified to pH=3 by addition of hydrochloric acid
  8. extractionextracted with ethyl acetate (300 mL×3)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-7c7132b21ded43f383de4afa0841124e
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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