Diisopropylcarbodiimide → 4-(4-Iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide

HRID 2180192Notes

Reaction equation

HRID 2180192 reaction equation
N1C=CC=CC=1.[I:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2([C:21]([OH:23])=O)[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.[Cl:24][C:25]1[CH:26]=[C:27]([NH:32]C2C=CC=CC=2)[CH:28]=[C:29]([Cl:31])[CH:30]=1.CC(C)N=C=NC(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:24][C:25]1[CH:26]=[C:27]([NH:32][C:21]([C:14]2([C:11]3[CH:10]=[CH:9][C:8]([I:7])=[CH:13][CH:12]=3)[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH2:19]2)=[O:23])[CH:28]=[C:29]([Cl:31])[CH:30]=1

Participants

6

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 190041313,5-Dichloro-N-phenylanilineHCID 685340374-(4-Iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid pyridine salt

Product 1

HCID 865871764-(4-Iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amideYield 34.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid pyridine salt (440 mg, 1.04 mmol, see Example 6) and 3,5-dichlorophenylaniline (0.20 g, 1.24 mmol, 1.2 eq.) in anhydrous DMF (5 mL) was added DIC (0.326 mL, 2.08 mmol, 2 eq.) followed by DMAP (0.006 g, 0.052 mmol, 5 mol %). The mixture was stirred at room temperature for 16 h and then it was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL). The organic layer was separated, washed with H2O (3×40 mL) and saturated brine (50 mL), dried over Na2SO4, filtered and concentrated by rotary evaporation. The crude material was purified by silica gel chromatography by eluting with 10% MeOH/EtOAc to give 175 mg (34%) of 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide as a white solid. MS(ESI): 489.1/491.1.

Workup

  1. customit was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL)
  2. customThe organic layer was separated
  3. washwashed with H2O (3×40 mL) and saturated brine (50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customThe crude material was purified by silica gel chromatography
  8. washby eluting with 10% MeOH/EtOAc

Sources & evidence

ORD record
ord-2e6b5e932e70485487d7575f37d06da7
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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