Acetic Acid → HCID 67323870, compound

HRID 1257630Notes

Reaction equation

HRID 1257630 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][C:9](=O)[CH2:8][C:7]1=[O:13].[CH:20]([NH2:33])([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[CH:20]([NH:33][CH:9]1[CH2:10][CH2:11][N:6]([CH2:5][C:4]2[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:3]=2[O:2][CH3:1])[C:7](=[O:13])[CH2:8]1)([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 7036BenzhydrylamineHCID 24436Sodium SulfateHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 497600861-[(2,4-Dimethoxyphenyl)methyl]piperidine-2,4-dione

Product 1

HCID 67323870HCID 67323870, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(2,4-dimethoxy-benzyl)-piperidine-2,4-dione (2.63 g, 10.0 mmol), benzhydrylamine (1.72 mL, 10.0 mmol) and sodium sulfate (5 g) in acetic acid (2.29 mL, 40.0 mmol) and DCM (40 mL) was stirred at ambient temperature for 6 hours before the addition of sodium triacetoxyborohydride (3.18 g, 15.0 mmol). The resulting mixture was stirred for 18 hours then filtered through Celite®, the filtrate washed with brine then dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 2.5% methanol in DCM). The residue was re-dissolved in acetic acid (300 μL) and methanol (30 mL) and treated with sodium cyanoborohydride (1.46 g, 23.2 mmol) and the resulting mixture stirred at ambient temperature for 18 hours. The mixture was concentrated under vacuum, the residue dissolved in DCM and washed with saturated aqueous sodium bicarbonate. The organic phase was dried over sodium sulfate and concentrated under vacuum to afford 3.3 g (77%) of racemic 4-(benzhydryl-amino)-1-(2,4-dimethoxy-benzyl)-piperidin-2-one as an oil. LCMS (Method H, ESI): RT=2.47 min, m+H=431.3; 1H NMR (400 MHz, CDCl3) δ: 7.31 (m, 13H), 6.41 (s, 2H), 4.64 (d, 1H), 4.40 (d, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 3.32 (m, 1H), 3.13-3.05 (m, 1H), 2.95 (m, 1H), 2.72 (dd, 1H), 2.30 (dd, 1H), 2.02-1.92 (m, 1H), 1.74-1.57 (m, 1H).

Workup

  1. filtrationthen filtered through Celite®
  2. washthe filtrate washed with brine
  3. dry with materialthen dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 2.5% methanol in DCM)
  6. dissolutionThe residue was re-dissolved in acetic acid (300 μL)
  7. stirringthe resulting mixture stirred at ambient temperature for 18 hours
  8. concentrationThe mixture was concentrated under vacuum
  9. dissolutionthe residue dissolved in DCM
  10. washwashed with saturated aqueous sodium bicarbonate
  11. dry with materialThe organic phase was dried over sodium sulfate
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5d04cbe30c524bd4949643423507bcf9
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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