3-bromo-4-chloro-N-{(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-N-methyl-benzamide → 4-Chloro-N-{(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-3-ethyl-N-methyl-benzamide

HRID 1951151Notes

Reaction equation

HRID 1951151 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][C:38]=1[Cl:39])[C:5]([N:7]([CH:9]1[CH:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:12][N:11]([C:22]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]([C:32]3([CH3:35])[CH2:34][CH2:33]3)=[O:31])[CH2:26][CH2:25]2)=[O:23])[CH2:10]1)[CH3:8])=[O:6].[CH2:40]([Zn]CC)[CH3:41]>C1COCC1.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>[Cl:39][C:38]1[CH:37]=[CH:36][C:4]([C:5]([N:7]([CH:9]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=3)[CH2:12][N:11]([C:22]([CH:24]3[CH2:29][CH2:28][N:27]([C:30]([C:32]4([CH3:35])[CH2:34][CH2:33]4)=[O:31])[CH2:26][CH2:25]3)=[O:23])[CH2:10]2)[CH3:8])=[O:6])=[CH:3][C:2]=1[CH2:40][CH3:41]

Participants

5

Reactant 2

HCID 670256993-bromo-4-chloro-N-{(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-N-methyl-benzamideHCID 178418750HCID 178418750, compound

Product 1

HCID 670256714-Chloro-N-{(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-3-ethyl-N-methyl-benzamideYield 80.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-bromo-4-chloro-N-{(3RS,4SR)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-N-methyl-benzamide (50 mg; 0.076 mmol) in THF (0.5 mL) was added under an argon atmosphere tetrakis(triphenylphosphine)palladium (0) (5 mg; 0.04 mmol) and diethylzinc (1 M in hexane, 762 μL; 0.762 mmol). The resulting solution was stirred for 5 h at 65° C. before it was diluted with ethyl acetatec (30 mL) and washed with aqueous sodium carbonate (saturated, 20 mL), water (20 mL) and aqueous sodium carbonate. (saturated, 20 mL). The aqueous phases were extracted with ethyl acetate (30 mL) and dried over sodium sulfate. Purification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 90:10) afforded the title compound (37 mg, 47%) as a light brown foam. MS m/e: 604.2 [M]+.

Workup

  1. additionwas diluted with ethyl acetatec (30 mL)
  2. washwashed with aqueous sodium carbonate (saturated, 20 mL), water (20 mL) and aqueous sodium carbonate
  3. extractionThe aqueous phases were extracted with ethyl acetate (30 mL)
  4. dry with materialdried over sodium sulfate
  5. customPurification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 90:10)

Sources & evidence

ORD record
ord-a0baef209a0f4b898bb761609ad6aaed
Source dataset
uspto-grants-2013_03
Patent number
US08404679B2

Reaction notes

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