Hydrochloric Acid → 1-(3-Aminopropyl)-4-diphenylmethylpiperidine

HRID 322167Notes

Reaction equation

B.O1CCCC1.[C:7]1([CH:13]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][C:22]#[N:23])[CH2:16][CH2:15]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.[OH-].[Na+]>>[NH2:23][CH2:22][CH2:21][CH2:20][N:17]1[CH2:18][CH2:19][CH:14]([CH:13]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:15][CH2:16]1

Participants

Reactant 4

HCID 313Hydrochloric Acid

HCID 14798Sodium Hydroxide

HCID 2723981Borane;tetrahydrofuran

HCID 230041313-(4-Diphenylmethylpiperidin-1-yl)propionitrile

Product 1

HCID 230041171-(3-Aminopropyl)-4-diphenylmethylpiperidineYield 86.2%

Conditions

Temperature: 0 °C

Procedure

Borane-tetrahydrofuran complex (1.0M in THF, 5.5 mL, 5.5 mmol, 3.5 equiv) was added under argon to neat 3-(4-diphenylmethylpiperidin-1-yl)propionitrile (480 mg, 1.58 mmol, 1.00 equiv). The mixture was stirred at reflux for 5 hours and then cooled to 0° C. Aqueous HCl (6N, 6 mL) was added cautiously, and stirring was continued at room temperature overnight, then at 42° C. for 1.5 hours. The solution was basified to pH 10-11 by addition of 6N aqueous NaOH and extracted with CH2Cl2 (3×50 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, CHCl3—MeOH—NH3 (2.0M in MeOH) to give 420 mg (86%) of colorless oil, which was characterized spectroscopically.

Workup

temperatureat reflux for 5 hours
stirringstirring
waitat 42° C. for 1.5 hours
extractionextracted with CH2Cl2 (3×50 mL)
dry with materialThe combined organic solutions were dried over MgSO4
concentrationconcentrated
customThe residue was purified by flash chromatography (SiO2, CHCl3—MeOH—NH3 (2.0M in MeOH)

Sources & evidence

ORD record: ord-621a98c99f814eb68f604467623b1ed1
Source dataset: uspto-grants-2001_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06211198B1

Reaction notes

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