Hydrogen chloride-ethyl acetate → N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-(piperidin-4-ylcarbonyl)piperidin-4-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide Monohydrochloride

HRID 1260932Notes

Reaction equation

HRID 1260932 reaction equation
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH3:45])[C@@H:16]2[CH2:21][CH2:20][N:19]([C:22]([CH:24]3[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]3)=[O:23])[CH2:18][C@H:17]2[C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=2)=[O:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.C(OCC)(=O)C>C(OCC)(=O)C>[ClH:43].[Cl:44][C:39]1[CH:38]=[C:37]([C@H:17]2[C@H:16]([N:15]([CH3:45])[C:13](=[O:14])[C:5]3[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=[C:3]([C:2]([F:46])([F:1])[F:47])[CH:4]=3)[CH2:21][CH2:20][N:19]([C:22]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[O:23])[CH2:18]2)[CH:42]=[CH:41][C:40]=1[Cl:43]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetate2×HCID 86631298HCID 86631298, compound

Product 1

HCID 86631339N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-(piperidin-4-ylcarbonyl)piperidin-4-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide MonohydrochlorideYield 177.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl 4-{[(3R,4R)-4-[{[3,5-bis(trifluoromethyl)phenyl]carbonyl}(methyl)amino]-3-(3,4-dichlorophenyl)piperidin-1-yl]carbonyl}piperidine-1-carboxylate (0.502 g) obtained in Example 87 in ethyl acetate (5 mL) was added 4N hydrogen chloride/ethyl acetate (4 mL), and the mixture was stirred at 50° C. for 2 hr. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate. This was washed with 1N aqueous sodium hydroxide solution and dried, and the solvent was evaporated under reduced pressure. The obtained residue was treated with 1 equivalent of 4N hydrogen chloride/ethyl acetate to give the title compound (0.405 g, 89%) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washThis was washed with 1N aqueous sodium hydroxide solution
  4. customdried
  5. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-c6b0e2f86ba040f3a81ab71411cca828
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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