Potassium Phosphate, Tribasic → 4-Cyclopropyl-2-chloro-3,5-difluoroaniline

HRID 1270730Notes

Reaction equation

Br[C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[C:4]([Cl:10])[C:3]=1[F:11].[CH:12]1(B(O)O)[CH2:14][CH2:13]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:12]1([C:2]2[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[C:4]([Cl:10])[C:3]=2[F:11])[CH2:14][CH2:13]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-bromo-2-chloro-3,5-difluoroaniline (5.35 g, 22.0 mmol), cyclopropylboronic acid (2.20 g, 24.0 mmol), K3PO4 (16 g, 78 mmol) and tricyclohexyl phosphine (0.623 g, 2.24 mmol) in toluene (30 mL) and water (8 mL) is degassed with N2 and heated to 100° C. Pd(OAc)2 (0.25 g, 1.16 mmol) is added. The reaction mixture is heated to 100° C. overnight, cooled and loaded directly on a column of silica gel. The residue is purified by column chromatography (EtOAc/hexanes) to give 4-cyclopropyl-3,5-difluoro-2-chloroaniline.

Workup

customis degassed with N2
temperatureThe reaction mixture is heated to 100° C. overnight
temperaturecooled
customThe residue is purified by column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-b937d98ed8b94148bb9dc3bd98cf28e0
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07202364B2

Reaction notes

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