Acetic Acid → tert-Butyl methyl(1-((2-(pyrrolidin-1-yl)pyridin-4-yl)methyl)piperidin-4-yl)carbamate

HRID 1193317Notes

Reaction equation

HRID 1193317 reaction equation
[CH3:1][N:2]([CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[N:16]1([C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][N:28]=2)[CH:24]=O)[CH2:20][CH2:19][CH2:18][CH2:17]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl>[CH3:1][N:2]([CH:10]1[CH2:11][CH2:12][N:13]([CH2:24][C:23]2[CH:26]=[CH:27][N:28]=[C:21]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH:22]=2)[CH2:14][CH2:15]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 27568064-N-Boc-4-N-Methyl-aminopiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 185258452-(Pyrrolidin-1-yl)isonicotinaldehyde

Product 1

HCID 66805506tert-Butyl methyl(1-((2-(pyrrolidin-1-yl)pyridin-4-yl)methyl)piperidin-4-yl)carbamateYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl methyl(piperidin-4-yl)carbamate (2.333 mmol, 1 eq) and 2-(pyrrolidin-1-yl)-isonicotinaldehyde (2.66 mmol, 1.14 eq) were dissolved in dichloromethane (15 ml), and acetic acid (5.459 mmol, 2.34 eq) and sodium triacetoxyborohydride (3.266 mmol, 1.4 eq) were added. The reaction mixture was stirred for 48 h at RT. When the reaction was complete (TLC monitoring), sat. sodium hydrogen carbonate solution was added to the reaction mixture and the phases were separated. The aqueous phase was extracted with dichloromethane (2×30 ml). The combined organic phases were washed with sat. NaCl solution, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography (silica gel, ethyl acetate:cyclohexane 2:1). Yield: 64%.

Workup

  1. additionwas added to the reaction mixture
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with dichloromethane (2×30 ml)
  4. washThe combined organic phases were washed with sat. NaCl solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (silica gel, ethyl acetate:cyclohexane 2:1)

Sources & evidence

ORD record
ord-95c29457851b41b49df1794a0a560518
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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