Aniline → tert-butyl 4-(2-chloro-5-fluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 2054740Notes

Reaction equation

HRID 2054740 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[CH:13]=[CH:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]1.F[B-](F)(F)F.[C:26]1([N+]#N)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.NC1C=CC=CC=1.O.O.O.C([O-])(=O)C.[Na+]>C(#N)C.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]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:12]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:13]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 5284485Benzenediazonium tetrafluoroborateHCID 23665404Sodium Acetate TrihydrateHCID 58641400tert-butyl 3-(2-chloro-5-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 59656605tert-butyl 4-(2-chloro-5-fluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (20 mg, 022 mmol, 0.020 equiv) was added to a deoxygenated mixture of tert-butyl 3-(2-chloro-5-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate (1-2,330 mg, 1.11 mmol, 1 equiv), benzenediazonium tetrafluoroborate (1-3, prepared from aniline by the method described for 1-1, 213 mg, 1.11 mmol, 1.00 equiv), and sodium acetate trihydrate (459 mg, 3.32 mmol, 3.00 equiv) in acetonitrile (20 mL) at 23° C. The reaction mixture was stirred for 16 h, then partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (2×70 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 40% hexanes in EtOAc) to provide tert-butyl 4-(2-chloro-5-fluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (14) as a dark orange oil. LRMS m/z (M+H—CH3) 359.0 found, 359.1 required.

Workup

  1. customat 23° C
  2. custompartitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (2×70 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (hexanes initially

Sources & evidence

ORD record
ord-985ed57953ae4527b2ae022a06cc4720
Source dataset
uspto-grants-2008_02
Patent number
US07329762B2

Reaction notes

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