4-Bromoaniline → 5-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carbonitrile
Reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH3:9][N:10]1[C:14]([C:15]#[N:16])=[CH:13][CH:12]=[C:11]1B(O)O.[F-].[K+]>CCOC(C)=O.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].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:11]2[N:10]([CH3:9])[C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)=[CH:3][CH:4]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 25 °C
Procedure
4-Bromoaniline (5.00 g, 29.0 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (5.2 g, 34.8 mmol), KF (5.55 g, 95.7 mmol), and Pd2(dba)3 (332 mg, 0.36 mmol) were added to a 200 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 min. THF (72 mL) was added and the mixture was purged with nitrogen for an additional 5 min. A solution of tri-t-butylphosphine (10 wt % in hexanes) (2.15 mL, 0.73 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 5 h. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed through with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification by silica gel flash chromatography (20% acetone/hexane) afforded 5-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carbonitrile (3.3 g) as an off-white solid.
Workup
- customThe flask was sealed
- custompurged with nitrogen for 5 min
- additionTHF (72 mL) was added
- customthe mixture was purged with nitrogen for an additional 5 min
- filtrationfiltered through a plug of silica gel
- washwashed through with 200 mL of EtOAc
- concentrationconcentrated
- customto give a crude brown/black semi-solid
- customPurification by silica gel flash chromatography (20% acetone/hexane)
Sources & evidence
- ORD record
- ord-82735cae8fda401f9a4f5b5a53226cf1
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07652062B2
Reaction notes
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