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

HRID 1882960Notes

Reaction equation

HRID 1882960 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-toluene-sulfonate (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-237130d757534113be76afc8f1c2edc4
Source dataset
uspto-grants-2004_07
Patent number
US06759414B2

Reaction notes

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