Pyridine → N-Methoxy-N-methyl-4-pentylbenzamide

HRID 1635565Notes

Reaction equation

HRID 1635565 reaction equation
[CH2:1]([C:6]1[CH:14]=[CH:13][C:9]([C:10](O)=[O:11])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C(Cl)(=O)C(Cl)=O.Cl.[CH3:22][NH:23][O:24][CH3:25].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C>[CH3:25][O:24][N:23]([CH3:22])[C:10](=[O:11])[C:9]1[CH:13]=[CH:14][C:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 334794-Pentylbenzoic acidHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 12052727N-Methoxy-N-methyl-4-pentylbenzamideYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-pentylbenzoic acid (5 g, 0.026 mol) in 260 ml of CH2Cl2 containing molecular sieves (4 Å), two drops of DMF was added, and then oxalyl chloride (5.45 g, 0.043 mol) was added dropwise. After stirring for 4.5 h the mixture was filtered, concentrated on the rotatory evaporator and pumped for 15 min. The residue was redissolved in 130 ml of CH2Cl2 and N,O-dimethylhydroxylamine HCl (3.04 g, 0.031 mol) was added at room temperature. After cooling the solution to 0° C., 5.3 ml of pyridine (0.065 mol) was added and the solution was stirred at 23° C. for 18 h. The solution was concentrated on the rotatory evaporator and the residue was partitioned between brine and a mixture of ether and CH2Cl2 (1:1). The organic layer was separated, dried and concentrated to yield 5.9 g (98%) of 2, which was used without further purification in the subsequent step. 1H NMR (100 MHz, CDCl3) δ 0.9 (t, 3H), 1.45 (m, 6H), 2.6 (t, J=6.4 Hz, 2H), 3.3 (s, 3H), 3.5 (s, 3H), 7.2 (d, J=8.0 Hz, 2H), 7.6 (d, J=8.2 Hz, 2H).

Workup

  1. filtrationwas filtered
  2. concentrationconcentrated on the rotatory evaporator
  3. waitpumped for 15 min
  4. dissolutionThe residue was redissolved in 130 ml of CH2Cl2
  5. stirringthe solution was stirred at 23° C. for 18 h
  6. concentrationThe solution was concentrated on the rotatory evaporator
  7. customthe residue was partitioned between brine
  8. additiona mixture of ether and CH2Cl2 (1:1)
  9. customThe organic layer was separated
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-9131dcf69379477ab51801e864e722ac
Source dataset
uspto-grants-2003_01
Patent number
US06509367B1

Reaction notes

Loading…