Water → 2-(1-Boc-piperidin-4-ylmethylidene)amino-N-(5-chloropyridin-2-yl)-5-fluorobenzamide

HRID 988629Notes

Reaction equation

HRID 988629 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C:17]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:18]=1[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=1)=[O:20].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.O>C1C=CC=CC=1>[C:1]([N:8]1[CH2:9][CH2:10][CH:11]([CH:14]=[N:16][C:17]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=2)=[O:20])[CH2:12][CH2:13]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 962WaterHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 219063152-amino-N-(5-chloropyridin-2-yl)-5-fluorobenzamide

Product 1

HCID 219061692-(1-Boc-piperidin-4-ylmethylidene)amino-N-(5-chloropyridin-2-yl)-5-fluorobenzamideYield 93%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution containing 1-Boc-piperidine-4-carboxaldehyde (3.0 g, ca. 14 mmol), 2-amino-N-(5-chloropyridin-2-yl)-5-fluorobenzamide (3.7 g, 14 mmol), and pyridinium p-toluenesulfonate (0.3 g, 1.4 mmol) in benzene (250 mL) was heated at reflux for 24 h with azeotropic removal of water. The solution was allowed to cool to room temperature; then the solvent was removed in vacuo and the residue was partitioned between ethyl acetate (300 mL) and water (150 mL). The organic phase was separated and washed again with water (150 mL) and then brine (150 mL); then dried with MgSO4, filtered and concentrated in vacuo to give 6.0 g (93%) of the title compound as an orange foam which was used directly in the next step without further purification.

Workup

  1. temperaturewas heated
  2. customthen the solvent was removed in vacuo
  3. customthe residue was partitioned between ethyl acetate (300 mL) and water (150 mL)
  4. customThe organic phase was separated
  5. washwashed again with water (150 mL)
  6. dry with materialthen dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a4799f1d332e4b068ee1875adf9b51a3
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

Loading…