Hydrochloric Acid → HCID 72695026, compound

HRID 1476745Notes

Reaction equation

HRID 1476745 reaction equation
[O:1]([CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]1[C:16]([NH:18][C@H:19]([C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=1)[CH3:20])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[ClH:33]>C1COCC1.CO>[ClH:33].[O:1]([CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]1[C:16]([NH:18][C@H:19]([C:21]1[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:29][CH:30]=1)[CH3:20])=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86707209HCID 86707209, compound

Product 1

HCID 72695026HCID 72695026, compoundYield 66.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve methyl 4-[(1S)-1-[[(2R)-1-(2-phenoxyethyl)piperidine-2-carbonyl]amino]ethyl]benzoate (930 mg, 2.27 mmol) in THF (4.0 mL) and CH3OH (4.0 mL) at room temperature. Add NaOH (1 M aqueous solution, 4.5 mL, 4.5 mmol), then stir the resulting mixture at room temperature for three days. Concentrate the reaction mixture under reduced pressure to furnish a gummy solid. Add hydrogen chloride (4 M solution in dioxane, 2 mL, 8 mmol), and stir vigorously for 10 minutes. Remove the suspended solids by filtration, and concentrate the filtrate under reduced pressure to furnish a white solid. Triturate the solid in boiling diethyl ether (25 mL), and isolate the suspended solids by filtration to furnish the title compound (650 mg, 66% yield) as a white solid. Mass spectrum (m/z): 397 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 12.89 (br s, 1H), 10.08 (br s, 1H), 9.41 (d, J=7.6 Hz, 1H), 7.88 (d, J=8.2 Hz, 2H), 7.47 (d, J=8.2 Hz, 2H), 7.26 (dd, J=8.4, 7.6 Hz, 2H), 6.96 (t, J=7.2 Hz, 1H), 6.90 (d, J=7.9 Hz, 2H), 5.02 (app pentet, J=7.1 Hz, 1H), 4.34-4.21 (m, 2H), 4.03 (app t, J=10.2 Hz, 1H), 3.57 (d, J=12.4 Hz, 1H), 3.48-3.39 (m, 1H), 3.37-3.18 (m, 2H), 2.15 (d, J=13.5 Hz, 1H), 1.82-1.66 (m, 4H), 1.50-1.43 (m, 1H), 1.39 (d, J=7.2 Hz, 3H).

Workup

  1. concentrationConcentrate the reaction mixture under reduced pressure
  2. customto furnish a gummy solid
  3. customRemove the suspended solids
  4. filtrationby filtration
  5. concentrationconcentrate the filtrate under reduced pressure
  6. customto furnish a white solid
  7. customTriturate the solid
  8. customisolate the suspended solids
  9. filtrationby filtration

Sources & evidence

ORD record
ord-9543973a22b847f68945969d1db3c977
Source dataset
uspto-grants-2016_08
Patent number
US09402838B2

Reaction notes

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