Ethanol → 4-(3'-Cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide

HRID 2180193Notes

Reaction equation

HRID 2180193 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2([C:19]3[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=3)[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:26]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)#[N:27].C([O-])([O-])=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2([C:19]3[CH:24]=[CH:23][C:22]([C:32]4[CH:31]=[CH:30][CH:29]=[C:28]([C:26]#[N:27])[CH:33]=4)=[CH:21][CH:20]=3)[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 865871764-(4-Iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide

Product 1

HCID 207794484-(3'-Cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amideYield 400%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a flask containing 4-(4-iodo-phenyl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide (175 mg, 0.35 mmol) was added Pd(PPh3)4 (13 mg, 0.035 mmol, 10 mol %), 3-cyanophenylboronic acid (78 mg, 0.53 mmol, 1.5 eq.) and Na2CO3 (0.53 g, 5 mmol). The mixture was suspended in toluene (5 mL), EtOH (2.5 mL) and H2O (2.5 mL) and heated at 90° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation. The crude product was purified by HPLC to give 4-(3′-cyano-biphenyl-4-yl)-1-methyl-piperidine-4-carboxylic acid (3,5-dichloro-phenyl)-amide as a white solid (0.066 g, 1.4 mmol, 14%). 1H NMR (300 MHz, CDCl3): δ 7.95 (M, 1H), 7.91 (M, 1H), 7.62 to 7.76 (m, 6H), 7.51 (d, 2H), 7.19 (br, 1H), 7.15 (t, 1H), 2.71 (m, 6H), 2.42 (s, 3H), 2.30 (m, 2H). MS (ESI): 464.2/466.2 (M+1).

Workup

  1. custompartitioned between EtOAc (10 mL) and saturated Na2CO3 (5 mL)
  2. washThe organic layer was washed with saturated Na2CO3 (3×5 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-dbe1549e6daa4a8abfbce86bc4a43ea3
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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