({3-[(3-Bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)amine → ({4-Chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)amine

HRID 1875168Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:19])=[C:12]([CH2:17][NH2:18])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Br-].[CH:21]1([Zn+])[CH2:23][CH2:22]1>C1COCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:16][C:15]1[CH:14]=[CH:13][C:12]([CH2:17][NH2:18])=[C:11]([F:19])[C:10]=1[O:9][C:4]1[CH:3]=[C:2]([CH:21]2[CH2:23][CH2:22]2)[CH:7]=[C:6]([Cl:8])[CH:5]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of ({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)amine (0.460 g, 1.260 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.029 g, 0.025 mmol) in THF (10 ml) was added cyclopropylzinc bromide (0.5 M solution in THF) (6.30 ml, 3.15 mmol) and the reaction mixture was stirred at 60° C. for 1 hour. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give ({4-chloro-3-[(3-chloro-5-cyclopropylphenyl)oxy]-2-fluorophenyl}methyl)amine (0.281 g, 0.861 mmol, 68% yield). 1H NMR (400 MHz, METHANOL-d4) d ppm 7.20-7.44 (m, 3H), 6.76 (s, 1H), 6.54 (s, 1H), 3.86 (s, 2H), 1.74-2.05 (m, 1H), 0.83-1.08 (m, 2H), 0.40-0.76 (m, 2H).

Workup

washwashed with water
customThe solvent was removed
customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record: ord-9928764cddf8461db0ab33ba210950d8
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304419B2

Reaction notes

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