Sodium Hydroxide → HCID 178455816, compound

HRID 525437Notes

Reaction equation

HRID 525437 reaction equation
[CH2:1]([C@@H:3]1[CH2:8][CH2:7][C@H:6]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([CH2:20][N:21]2[CH2:26][CH2:25][CH:24]([C:27]([O:29]CC)=[O:28])[CH2:23][CH2:22]2)[CH:14]=[CH:13]3)[CH2:5][CH2:4]1)[CH3:2].[OH-].[Na+]>C(O)C.O>[CH2:1]([C@@H:3]1[CH2:4][CH2:5][C@H:6]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([CH2:20][N:21]2[CH2:22][CH2:23][CH:24]([C:27]([OH:29])=[O:28])[CH2:25][CH2:26]2)[CH:14]=[CH:13]3)[CH2:7][CH2:8]1)[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 178469206HCID 178469206, compound

Product 1

HCID 178455816HCID 178455816, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of ethyl 1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylate (1.6 g, 0.004 mol, 1.0 eq) and NaOH (0.48 g, 0.012 mol, 3.0 eq) in ethanol (10 mL) and water (2 mL) was refluxed for 2 h. After the solvent was removed in vacuo, the residue was dissolved in water (20 mL) and acidified with 1 N HCl to pH=7. The mixture was extracted with dichloromethane (50 mL*3) and the combined organic layers were washed with brine (30 mL), dried over sodium sulfate, concentrated and recrystallized in ethyl acetate to give 1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid (1.1 g, yield: 71%) as a white solid. ESI-MS (M+H)+: 396.3. HPLC: 100%. 1H NMR (400 MHz, DMSO-d6) δ: 7.77 (d, J=9.2 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H) 7.63 (s, 1H), 7.39 (dd, J=8.4, 1.2 Hz, 1H), 7.29 (d, J=2.0 Hz, 1H), 7.15 (dd, J=8.8, 2.4 Hz, 1H), 4.71-4.69 (m, 1H), 3.54 (s, 2H), 2.78-2.74 (m, 2H), 2.16-2.15 (m, 1H), 2.01-1.93 (m, 4H), 1.77-1.75 (m, 2H), 1.63-1.50 (m, 6H), 1.34-1.24 (m, 5H), 0.87 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturewas refluxed for 2 h
  2. customAfter the solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in water (20 mL)
  4. extractionThe mixture was extracted with dichloromethane (50 mL*3)
  5. washthe combined organic layers were washed with brine (30 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customrecrystallized in ethyl acetate

Sources & evidence

ORD record
ord-6d2d7b1ac36043c88a35b5e3ec5cabce
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

Loading…