Hydrochloric Acid → 3-Piperidinamine, N,4-dimethyl-1-(phenylmethyl)-, hydrochloride (1:2)

HRID 2114003Notes

Reaction equation

HRID 2114003 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[CH:10]([NH:15][CH3:16])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:17]>C1(C)C=CC=CC=1.C(O)C.O>[ClH:17].[ClH:17].[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[CH:10]([NH:15][CH3:16])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 99438891-benzyl-N,4-dimethylpiperidin-3-amine

Product 1

HCID 99438883-Piperidinamine, N,4-dimethyl-1-(phenylmethyl)-, hydrochloride (1:2)Yield 62%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 23.4 kg of (1-benzyl-4-methylpiperidin-3-yl)-methylamine in 10 liters of toluene and 120 liters of ethanol at 3° C. was added 25 liters of 32% HCl in water, keeping the reaction temperature below 10° C. 100 liters of solvent was distilled off under partial vacuum, and 215 liters of ethyl acetate was added at 30° C. 210 liters of solvent was distilled off under partial vacuum, and a second 215 liters of ethyl acetate was added and another 210 liters of solvent was distilled off under partial vacuum. 111 liters of acetone was added at 35 C°, the suspension was cooled to 0° C., and then the product, (1-benzyl-4-methylpiperidin-3-yl)-methylamine bishydrochloride, was filtered off and washed with 55 liters of acetone. The wet-cake was reslurried 3 times in ethanol (10 volume equivalents at reflux) to upgrade the diasteromeric ratio of cis:trans from 91:9 to greater than 97:3. Total recovery was 19.4 kg, 62% yield. 1H NMR (CD3OD, 400 MHz): 7.55 (m, 5H), 4.88 (s, 3H), 4.52 (d, J=12.8 Hz, 1H), 4.45 (d, J=12.8 Hz, 1H), 3.76 (m, 1H), 3.67 (m, 1H), 3.40-3.00 (m, 3H), 2.78 (3, 3H), 2.55 (m, 1H), 2.14 (m, 1H), 1.90 (m, 1H), 1.16 (d, J=7.2 Hz, 3H)

Workup

  1. customthe reaction temperature below 10° C
  2. distillation100 liters of solvent was distilled off under partial vacuum, and 215 liters of ethyl acetate
  3. additionwas added at 30° C
  4. distillation210 liters of solvent was distilled off under partial vacuum
  5. additiona second 215 liters of ethyl acetate was added
  6. distillationanother 210 liters of solvent was distilled off under partial vacuum
  7. addition111 liters of acetone was added at 35 C°
  8. filtrationthe product, (1-benzyl-4-methylpiperidin-3-yl)-methylamine bishydrochloride, was filtered off
  9. washwashed with 55 liters of acetone

Sources & evidence

ORD record
ord-998554e435b3421d836e83ff5a9322f5
Source dataset
uspto-grants-2008_10
Patent number
US07432370B2

Reaction notes

Loading…