Acetic Acid → HCID 10092832, compound

HRID 2103735Notes

Reaction equation

HRID 2103735 reaction equation
[CH2:1]([N:3]([CH2:26][CH3:27])[C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([N:11]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:7][CH:6]=1)[CH3:2].[CH3:28][C:29]([CH3:31])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[CH2:26]([N:3]([CH2:1][CH3:2])[C:4](=[O:25])[C:5]1[CH:6]=[CH:7][C:8]([N:11]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:12]2[CH2:17][CH2:16][N:15]([CH:29]([CH3:31])[CH3:28])[CH2:14][CH2:13]2)=[CH:9][CH:10]=1)[CH3:27]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 10406550HCID 10406550, compound2×

Product 1

HCID 10092832HCID 10092832, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N,N-diethyl-4-[benzyl(piperidin-4-yl)amino]benzamide (Compound 8) (0.27 g, 0.739 mmole), acetone (0.09 g, 1.48 mmol), and acetic acid (0.04 g, 0.739 mmol) in 10 mL of dry dichloromethane was added sodium triacetoxyborohydride (0.31 g, 1.48 mmol) under nitrogen. The mixture was stirred for 40 hours, and then aqueous 1 N NaOH (20 mL) solution was added. After 1 h of stirring, the layers were separated, and the aqueous layer was extracted twice with dichloromethane (15 mL). The organic extracts were combined, washed twice with 1 N NaOH (20 mL), dried (Na2SO4), and concentrated to give a brown-black glass. This material was purified on a flash silica gel column (5% methanol-chloroform to 10% methanol-chloroform) to provide 0.13 g (43%) of N,N-diethyl-4-[benzyl(1-isopropylpiperidin-4-yl)amino]benzamide as a colorless oil. MS (ES), m/z 408 (MH+). 300 MHz 1H NMR (CDCl3) δ1.06 (d, J=6.4 Hz, 6H), 1.17 (t, J=7.0 Hz, 6H), 1.68-1.92 (m, 4H), 2.29 (br t, 2H), 2.69-2.85 (br m, 1H), 2.97 (br d, J=10.3 Hz, 2H), 3.32-3.52 (m, 4H), 3.74-3.89 (br m, 1H), 4.53 (s, 2H), 6.65 (d, J=8.8 Hz, 2H), 7.18-7.42 (m, 7H).

Workup

  1. stirringAfter 1 h of stirring
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted twice with dichloromethane (15 mL)
  4. washwashed twice with 1 N NaOH (20 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto give a brown-black glass
  8. customThis material was purified on a flash silica gel column (5% methanol-chloroform to 10% methanol-chloroform)

Sources & evidence

ORD record
ord-bd1d91b4e93242a7889a7c91ded8b564
Source dataset
uspto-grants-2009_08
Patent number
US07576105B2

Reaction notes

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