Dichloromethane → (4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

HRID 511070Notes

Reaction equation

HRID 511070 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=O)(C)(C)C.F[C:16]1[CH:17]=[CH:18][C:19]([N+:26]([O-:28])=[O:27])=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:35]CCl>CS(C)=O.C(OCC)C>[ClH:35].[N+:26]([C:19]1[CH:18]=[CH:17][C:16]([NH:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:21][C:20]=1[C:22]([F:23])([F:24])[F:25])([O-:28])=[O:27]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2230945-Fluoro-2-nitrobenzotrifluorideHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 66671805(4-Nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine hydrochloride

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (47.8 g; 0.23 mol), 5-fluoro-2-nitrobenzotrifluoride (50.0 g; 0.23 mol) and potassium carbonate (99.7 g; 0.69 mol) in dimethylsulfoxide (600 mL) is heated at 100° C. for 3.5 hours. The mixture is then diluted with dichloromethane (200 mL) and is washed aq. sat ammonium chloride (2×55 mL) and with brine (25 mL). The organic layer is then dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained is then dissolved in a minimum volume of diethylether and petrol ether is added until precipitation is observed. The precipitate is filtered, washed with petrol ether (10 mL) and dried under high vacuum to afford the desired product (75.4 g; 0.19 mol). The product is dissolved in a 1 to 1 mixture of dichloromethane and trifluoroacetic acid (600 mL) and the resulting solution is stirred at room temperature until complete conversion is observed. A 4N aq. solution of sodium hydroxide is added until the pH of the aqueous layer reaches 8-9. The organic phase is separated, dried over sodium sulfate, filtered and concentrated under vacuum. The residue obtained is diluted in diethylether (200 mL) and a molar solution of hydrochloric acid in diethylether (150 mL) is added. The precipitate obtained is filtered and dried under high vacuum to afford the desired product as hydrochloride (59.0 g; 0.18 mol).

Workup

  1. washis washed aq.
  2. dry with materialThe organic layer is then dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. additionis added until precipitation
  7. filtrationThe precipitate is filtered
  8. washwashed with petrol ether (10 mL)
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-ebf7878997694a5284b31730e8aaa31d
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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