p-Toluenesulfonic acid → HCID 19762423, compound

HRID 248915Notes

Reaction equation

HRID 248915 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:11][O:12][C:13]2[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=2)=[CH:3][CH:2]=1.[NH2:21][CH:22]1[CH2:27][CH2:26][N:25]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:24][CH2:23]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>C1(C)C=CC=CC=1.O>[C:29]1([CH2:28][N:25]2[CH2:26][CH2:27][CH:22]([NH:21][CH2:17][C:16]3[CH:19]=[CH:20][C:13]([O:12][CH2:11][C:4]4[C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:1]=[CH:2][CH:3]=4)=[CH:14][CH:15]=3)[CH2:23][CH2:24]2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 4158521-Benzyl-4-piperidylamineHCID 4311764Sodium borohydrideHCID 19762434HCID 19762434, compound

Product 1

HCID 19762423HCID 19762423, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 4-(4-quinolinylmethoxy)benzaldehyde (2.63 g, 10 mmol), 4-amino-1-benzylpiperidine (2.5 g, 13.1 mmol), and 4-toluenesulfonic acid (0.38 g, 2 mmol) was refluxed in toluene (500 mL) for 15 hours with azeotropic removal of water. The solvent was removed in vacuo, and the residue redissolved in MeOH. The stirred solution was treated with solid sodium borohydride (1 g, 26.5 mmol) at room temperature for 1 hour. The solvent was removed in vacuo, the residue redissolved in methylene chloride, and extracted with 1N NaOH (aq) (2×100 mL), and water(2×100 mL). The dried (MgSO4) organic phase was evaporated in vacuo and treated with etheral-hydrogen chloride(g) in methanol to afford the title compound (4.6 g, 9.0 mmol, 90% yield) as the dihydrochloride salt. The dihydrochloride salt was converted to the free base with 1N NaOH (aq) and extracted with methylene chloride. The organic phase was washed with water (2×75 mL), dried (MgSO4), evaporated in vacuo, and the residue crystallized from ether-hexane to afford, after drying in vacuo (6 hours at 45° C.) overnight, the free base of the title compound, m.p. 72°-75° C.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue redissolved in MeOH
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue redissolved in methylene chloride
  5. extractionextracted with 1N NaOH (aq) (2×100 mL), and water(2×100 mL)
  6. dry with materialThe dried (MgSO4) organic phase
  7. customwas evaporated in vacuo
  8. additiontreated with etheral-hydrogen chloride(g) in methanol

Sources & evidence

ORD record
ord-4fd0ab71b6a1452ba7be0839003d8f8e
Source dataset
uspto-grants-1993_05
Patent number
US05212182

Reaction notes

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