Trifluoroacetic acid → 4-Amino-1-(4-chloropyrimidin-2-yl)-4-methylpiperidine

HRID 1441017Notes

Reaction equation

HRID 1441017 reaction equation
C(OC([NH:8][C:9]1([CH3:22])[CH2:14][CH2:13][N:12]([C:15]2[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][N:16]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.[OH-].[Na+]>C(Cl)Cl>[NH2:8][C:9]1([CH3:22])[CH2:14][CH2:13][N:12]([C:15]2[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][N:16]=2)[CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 14798Sodium HydroxideHCID 196949254-t-Butoxycarbonylamino-1-(4-chloropyrimidin-2-yl)-4-methylpiperidine

Product 1

HCID 196949174-Amino-1-(4-chloropyrimidin-2-yl)-4-methylpiperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2.22 g (0.0068 mol) of 4-t-butoxycarbonylamino-1-(4-chloropyrimidin-2-yl)-4-methylpiperidine (step c) in 25 ml of anhydrous methylene chloride is cooled under a nitrogen atmosphere and 5 ml of anisole and 25 ml of trifluoroacetic acid are added slowly. The mixture is stirred for 1 hour at room temperature and 25 ml of a 30% solution of NaOH are added slowly. The reaction medium is extracted with methylene chloride and dried over Na2SO4 and the solvent and the anisole are evaporated off under reduced pressure. The residue is purified by chromatography using CH2Cl2 /MeOH=9/1 as the eluent to give 4- amino-1-(4-chloropyrimidin-2-yl)-4-methylpiperidine as the base, which is treated with maleic acid in an ethanol/isopropyl ether mixture. The maleate obtained in this way is isolated by filtration (m.p. 154°-155° C.).

Workup

  1. extractionThe reaction medium is extracted with methylene chloride
  2. dry with materialdried over Na2SO4
  3. customthe solvent and the anisole are evaporated off under reduced pressure
  4. customThe residue is purified by chromatography

Sources & evidence

ORD record
ord-5a86cdfada0e474e95764f561f235841
Source dataset
uspto-grants-1996_03
Patent number
US05502063

Reaction notes

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