1-Bromo-2,4-difluorobenzene → (2S,4S)-1-Boc-4-[(2,4-difluorophenyl)amino]-2[(dimethylamino)carbonyl]pyrrolidine

HRID 1361335Notes

Reaction equation

[C:1]([N:8]1[CH2:12][C@@H:11]([NH2:13])[CH2:10][C@H:9]1[C:14]([N:16]([CH3:18])[CH3:17])=[O:15])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.Br[C:47]1[CH:52]=[CH:51][C:50]([F:53])=[CH:49][C:48]=1[F:54]>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]>[C:1]([N:8]1[CH2:12][C@@H:11]([NH:13][C:47]2[CH:52]=[CH:51][C:50]([F:53])=[CH:49][C:48]=2[F:54])[CH2:10][C@H:9]1[C:14]([N:16]([CH3:18])[CH3:17])=[O:15])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of (2S,4S)-1-Boc-4-amino[(dimethylamino)carbonyl]pyrrolidine (8 g, 31.5 mmol) prepared in Step C in toluene (100 ml) was added sodium t-butoxide (3.46 g, 36 mmol), 2-(di-t-butylphosphino)biphenyl (800 mg, 2.68 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.6 g, 1.79 mmol) and 1-bromo-2,4-difluorobenzene (6.94 g, 36 mmol), and the solution was stirred at 110° C. for 10 h. After the reaction finished, the solution was filtered through Celite, and extracted with water and EtOAc. The organic layer was dried over MgSO4, concentrated in vacuo, and purified by column chromatography (eluent, EtOAc/Hex=1/4) to give the title compound (1.5 g, 78%).

Workup

filtrationthe solution was filtered through Celite
extractionextracted with water and EtOAc
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated in vacuo
custompurified by column chromatography (eluent, EtOAc/Hex=1/4)

Sources & evidence

ORD record: ord-8d6fcdda243c4b369bf8a8141f9acf90
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879852B2

Reaction notes

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