Acetic Acid → 4-(N-(2-methyl-3-phenyl-2-(E)-propenyl)aminomethyl)-1-t-butoxycarbonylpiperidine

HRID 2110824Notes

Reaction equation

HRID 2110824 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[CH3:16]/[C:17](=[CH:20]\[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)/[CH:18]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>O.CO.ClCCl.ClCCCl>[OH-:10].[NH4+:1].[CH3:16]/[C:17](=[CH:20]\[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)/[CH2:18][NH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

11

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 5372813alpha-METHYLCINNAMALDEHYDE

Product 2

HCID 14923Ammonium HydroxideYield 10%HCID 63395154-(N-(2-methyl-3-phenyl-2-(E)-propenyl)aminomethyl)-1-t-butoxycarbonylpiperidineYield 128.6%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-aminomethyl-1-t-butoxycarbonylpiperidine (3.6 g, 16.8 mmol), (E)-2-methyl-3-phenylpropenal (3.9 g, 26.7 mmol), acetic acid (3.9 g, 65 mmol), and 1,2-dichloroethane (30 mL) was stirred under argon at room temperature for 30 min before sodium triacetoxyborohydride (4.1 g, 19.3 mmol) was added. After 3 h saturated aqueous sodium bicarbonate was added to make the mixture basic, then it was diluted with water and extracted with dichloromethane (three times). The combined extracts were dried (anhydrous sodium sulfate) and evaporated under vacuum prior to column chromatography (silica gel, step-wise gradient of 2% to 4% of (10% concentrated aqueous ammonium hydroxide in methanol) in dichloromethane), which provided 4-(N-(2-methyl-3-phenyl-2-(E) -propenyl)aminomethyl)-1-t-butoxycarbonylpiperidine (3.72 g, 64% yield) as a pale yellow oil. A smaller excess of aldehyde over amine may produce optimal desired product yields when other aldehydes are used.

Workup

  1. additionwas added
  2. extractionextracted with dichloromethane (three times)
  3. dry with materialThe combined extracts were dried (anhydrous sodium sulfate)
  4. customevaporated under vacuum

Sources & evidence

ORD record
ord-6dc7a093d5714a33a292f6d6e2564d52
Source dataset
uspto-grants-2009_04
Patent number
US07517991B2

Reaction notes

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