Toluene → (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine

HRID 1868126Notes

Reaction equation

[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.[F:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>ClCCl.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:8][C:9]1[CH:10]=[CH:11][C:12]([N:6]2[CH2:5][CH2:4][NH:3][C@H:2]([CH3:1])[CH2:7]2)=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:14]=1

Participants

Conditions

Temperature: 110 °C

Procedure

(R)-2-methyl-piperazine (3.88 g, 38.70 mmol), 2-bromo, 5-fluoro benzotrifluoride (8.55 g, 35.18 mmol), tris(dibenzylidineacetone)dipalladium (0) (32.0 mg g, 0.35 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (657.0 mg, 1.06 mmol) and sodium tert-butoxide (5.07 g, 52.77 mmol) were charged to a reaction flask. Toluene (40 mL) was introduced under nitrogen atmosphere and the reaction mixture was heated up at 110° C. for 5.0 hours. Reaction was complete as determined by TLC. The reaction mixture was diluted with dichloromethane, washed with water, saturated brine then dried over MgSO4 and concentrated. The crude product was purified via flash column chromatography to yield (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine as a light brown oil (3.1 g, 33.6% yield).

Workup

customReaction
washwashed with water, saturated brine
dry with materialthen dried over MgSO4
concentrationconcentrated
customThe crude product was purified via flash column chromatography

Sources & evidence

ORD record: ord-9fadd48193674f86aee2834e1273fc9f
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07632838B2

Reaction notes

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