Hydrochloric Acid → HCID 11950910, compound

HRID 251460Notes

Reaction equation

HRID 251460 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:18][C:19](=[O:36])[C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH:31]3[CH3:35])=[CH:22][CH:21]=2)([C:14](OC)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Li+].[OH-].[Na+].Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.ClCCl.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:18][C:19](=[O:36])[C:20]2[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH:31]3[CH3:35])=[CH:24][CH:25]=2)([CH2:14][OH:15])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 11950908HCID 11950908, compound

Product 1

HCID 11950910HCID 11950910, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 1-benzyl-4-({4-[3-(2-methylpyrrolidin-1-yl)propoxy]benzoyl}amino)piperidine-4-carboxylate ax60 (0.93 g, 1.89 mmol) in dry tetrahydrofurane (20 ml) is cooled to 0° C. and lithium borohydride (1.4 ml, 2.83 mmol, 2 M in tetrahydrofurane) is added dropwise. The mixture is then stirred at room temperature overnight. The reaction mixture is then cooled to 0° C. and water (1.4 ml) and 1 N sodium hydroxide (1.4 ml) are added. After stirring for 20 minutes at 20° C., the mixture is concentrated and the residue is taken up in acetone (30 ml). The solution is cooled to 0° C., then 1 N hydrochloric acid (9.45 ml, 9.45 mmol) is added and the mixture is stirred at room temperature for 1 hour and concentrated to afford a pink oil. This oil is taken up in dichloromethane and treated with a saturated solution of potassium carbonate to reach pH 10. Dichloromethane is removed under reduced pressure and the aqueous phase is extracted twice with ethyl acetate. The combined organic extracts are dried over magnesium sulfate, filtered and concentrated to give 0.63 g of N-[1-benzyl-4-(hydroxymethyl)piperidin-4-yl]-4-[3-(2-methylpyrrolidin-1-yl)propoxy]benzamide ax62.

Workup

  1. temperatureThe reaction mixture is then cooled to 0° C.
  2. stirringAfter stirring for 20 minutes at 20° C.
  3. concentrationthe mixture is concentrated
  4. temperatureThe solution is cooled to 0° C.
  5. stirringthe mixture is stirred at room temperature for 1 hour
  6. concentrationconcentrated
  7. customto afford a pink oil
  8. customDichloromethane is removed under reduced pressure
  9. extractionthe aqueous phase is extracted twice with ethyl acetate
  10. dry with materialThe combined organic extracts are dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-af7cf884c92c4a8aae6ec16021b420ce
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

Loading…