Triethylamine → 1-{[4-(Aminomethyl)piperidin-1-yl)methyl]cyclobutanecarboxylic acid 4-methylbenzenesulfonate

HRID 16600Notes

Reaction equation

HRID 16600 reaction equation
C(OC([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2([C:21]([OH:23])=[O:22])[CH2:20][CH2:19][CH2:18]2)[CH2:12][CH2:11]1)=O)(C)(C)C.[CH3:24][C:25]1[CH:26]=[CH:27][C:28]([S:31]([OH:34])(=[O:33])=[O:32])=[CH:29][CH:30]=1.O.CCN(CC)CC>C1COCC1>[CH3:24][C:25]1[CH:26]=[CH:27][C:28]([S:31]([OH:34])(=[O:33])=[O:32])=[CH:29][CH:30]=1.[NH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2([C:21]([OH:23])=[O:22])[CH2:20][CH2:19][CH2:18]2)[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 521998p-Toluenesulfonic acid monohydrateHCID 672328231-[(4-{[(Tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]cyclobutanecarboxylic acid

Product 1

HCID 866021201-{[4-(Aminomethyl)piperidin-1-yl)methyl]cyclobutanecarboxylic acid 4-methylbenzenesulfonateYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a 500 mL, 3-necked round bottom flask under N2, a mixture of 1-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]cyclobutane carboxylic acid (30 g, 92 Step 6) in THF (150 mL) was stirred at room temperature for 10 min. To this suspension, a solution of p-TsOH H2O (52.4 g, 276 mmol) in THF (150 mL) was added at room temperature. After stirring at that temp for 10 min, the resulting solution was heated under reflux condition for 3 hrs. After cooling down to room temperature, Et3N (28.1 mL, 202 mmol) was added very slowly during the period of 1 h with seeding. The white precipitate was formed during the addition of Et3N. The resulting white suspension was stirred at room temperature for 6 h and it was filtered and the obtained solid was washed with THF (100 mL×2), dried at 50° C. for 5 h to give 35 g (96%) of the titled compound as white powder

Workup

  1. stirringAfter stirring at that temp for 10 min
  2. temperaturethe resulting solution was heated
  3. temperatureunder reflux condition for 3 hrs
  4. temperatureAfter cooling down to room temperature
  5. stirringThe resulting white suspension was stirred at room temperature for 6 h
  6. filtrationit was filtered
  7. washthe obtained solid was washed with THF (100 mL×2)
  8. customdried at 50° C. for 5 h

Sources & evidence

ORD record
ord-95a282202f63401e9e62900e77578a0b
Source dataset
uspto-grants-2010_06
Patent number
US07737163B2

Reaction notes

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