4-Fluoro-N-methylaniline → HCID 58191761, compound

HRID 1034616Notes

Reaction equation

HRID 1034616 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[C:5]([F:23])=[CH:4][N:3]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][CH3:32])=[CH:27][CH:26]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.O>[F:23][C:5]1[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])=[CH:7][C:2]([N:31]([C:28]2[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=2)[CH3:32])=[N:3][CH:4]=1

Participants

9

Reactant 4

HCID 680244-Fluoro-N-methylanilineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23665647Potassium tert-butoxideHCID 58191789HCID 58191789, compound

Product 1

HCID 58191761HCID 58191761, compoundYield 95%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 1-(2-chloro-5-fluoro-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (100 mg, 0.30 mmol) in toluene (25 mL) are added (4-fluoro-phenyl)-methyl-amine (48 mg, 0.39 mmol), 2-(dicyclohexylphosphino)-biphenyl (10 mg, 0.03 mmol), Pd2(dba)3 (14 mg, 0.015 mmol) and potassium tert-butoxide (84 mg, 0.75 mmol). The reaction mixture is stirred at 85° C. for 3 hours and cooled to room temperature. Water and EtOAc are added to the mixture. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by chromatography (EtOAc/hexane: 10%˜40%) to give (5-fluoro-4-{(S)-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-(4-fluoro-phenyl)-methyl-amine (120 mg, 95%). M/Z=424.23 [M+1]

Workup

  1. temperaturecooled to room temperature
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with EtOAc
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customThe crude product is purified by chromatography (EtOAc/hexane: 10%˜40%)

Sources & evidence

ORD record
ord-638d175d32d24927a3e14410cab2a1be
Source dataset
uspto-grants-2013_10
Patent number
US08546336B2

Reaction notes

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