Lithium Hydroxide → 2-(Cyclohexylmethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963128Notes

Reaction equation

HRID 1963128 reaction equation
[CH:1]1([CH2:7][CH:8]2[CH2:13][CH:12]([C:14]([O:16]C)=[O:15])[CH2:11][CH2:10][N:9]2[C:18]([O:20][CH3:21])=[O:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-]>C1COCC1.O>[CH:1]1([CH2:7][CH:8]2[CH2:13][CH:12]([C:14]([OH:16])=[O:15])[CH2:11][CH2:10][N:9]2[C:18]([O:20][CH3:21])=[O:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86646598Dimethyl 2-(cyclohexylmethyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667322852-(Cyclohexylmethyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dimethyl 2-(cyclohexylmethyl)piperidine-1,4-dicarboxylate (2.20 g, 7.40 mmol) was dissolved in THF (25 mL) and water (25 mL). LiOH (0.266 g, 11.1 mmol) was added and the resulting mixture was stirred at room temperature overnight and heated under reflux for 30 min. The reaction mixture was partitioned between 1 M KHSO4 and diethyl ether. The organic phase was dried (Na2SO4), filtered through Celite® and the solvent was evaporated. The crude product was dissolved again in THF (25 mL) and water (25 mL). LiOH (0.23 g) was added to the reaction flask. The reaction mixture was stirred overnight. The reaction was worked up as above to give the product. 1H NMR (600 MHz, cdcl3) δ 0.85 (ddd, 2H), 1.19 (dddd, 5H), 1.38-1.48 (m, 1H), 1.61 (d, 4H), 1.72 (tt, 2H), 1.97 (qd, 3H), 2.56-2.65 (m, 1H), 3.02-3.14 (m, 1H), 3.67 (d, 3H), 3.88 (d, 1H), 4.22 (s, 1H).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 30 min
  3. customThe reaction mixture was partitioned between 1 M KHSO4 and diethyl ether
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered through Celite®
  6. customthe solvent was evaporated
  7. dissolutionThe crude product was dissolved again in THF (25 mL)
  8. additionLiOH (0.23 g) was added to the reaction flask
  9. stirringThe reaction mixture was stirred overnight
  10. customto give the product

Sources & evidence

ORD record
ord-575fbe7982bb4b10ab8da3783db3f2bd
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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