Benzoic Acid → 4-Isopropylamino-1-(4-methoxypyrid-3-ylmethyl)piperidine monobenzoic acid salt

HRID 2101434Notes

Reaction equation

HRID 2101434 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:10]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:22]=[N:23][CH:24]=[CH:25][C:26]=2[O:27][CH3:28])[CH2:16][CH2:15]1)([CH3:12])[CH3:11]>C(OC)(C)(C)C>[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:10]([NH:13][CH:14]1[CH2:15][CH2:16][N:17]([CH2:20][C:21]2[CH:22]=[N:23][CH:24]=[CH:25][C:26]=2[O:27][CH3:28])[CH2:18][CH2:19]1)([CH3:12])[CH3:11]

Participants

4

Reactant 2

HCID 243Benzoic Acid2×HCID 11651846N-isopropyl-1-((4-methoxypyridin-3-yl)methyl)piperidin-4-amine

Product 1

HCID 674274674-Isopropylamino-1-(4-methoxypyrid-3-ylmethyl)piperidine monobenzoic acid saltYield 82.9%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

Benzoic acid (1451 g, 11.9 mol) and MTBE (5.8 L) were added to a 50 L 3-necked round-bottom flask equipped with a mechanical stirrer, thermometer, nitrogen inlet and heating mantle. The resulting slurry was heated at 45° C. to 50° C. to dissolve the benzoic acid. A solution of 4-isopropylamino-1-(4-methoxypyrid-3-ylmethyl)piperidine (3130 g, 11.9 mol) in methy tert-butyl ether (MTBE) (13.7 L) was added at 45° C. to 50° C. and the resulting mixture was stirred at reflux (50° C. to 55° C.) for 30 minutes and then at ambient temperature for 16 hours. The reaction mixture was then cooled to 0° C. to 5° C. with an ice/methanol bath and stirred for 30 minutes at which time a solid had formed. The solid was filtered through a polypropylene filter pad and washed with MTBE (3×2 L) and ethyl ether (3×2 L). The solid was then tray dried in a vacuum oven at room temperature until a constant weight was obtained to provide the title compound (3805 g, 82% yield).

Workup

  1. customequipped with a mechanical stirrer
  2. temperaturethermometer, nitrogen inlet and heating mantle
  3. temperatureThe resulting slurry was heated at 45° C. to 50° C.
  4. temperatureat reflux (50° C. to 55° C.) for 30 minutes
  5. temperatureThe reaction mixture was then cooled to 0° C. to 5° C. with an ice/methanol bath
  6. stirringstirred for 30 minutes at which time a solid
  7. customhad formed
  8. filtrationThe solid was filtered through a polypropylene
  9. filtrationfilter pad
  10. washwashed with MTBE (3×2 L) and ethyl ether (3×2 L)
  11. customtray dried in a vacuum oven at room temperature until a constant weight
  12. customwas obtained

Sources & evidence

ORD record
ord-413feeb9313e49baa6aa83e5bb789c56
Source dataset
uspto-grants-2009_08
Patent number
US07572918B2

Reaction notes

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