Binap, (A+-)- → 1-(4-(Difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine

HRID 2110139Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([F:11])[F:10])=[C:4]([CH3:12])[CH:3]=1.[CH3:13][C@H:14]1[CH2:19][NH:18][CH2:17][C@@H:16]([CH3:20])[NH:15]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:10][CH:9]([F:11])[O:8][C:5]1[CH:6]=[CH:7][C:2]([N:18]2[CH2:17][CH:16]([CH3:20])[NH:15][CH:14]([CH3:13])[CH2:19]2)=[CH:3][C:4]=1[CH3:12]

Participants

Conditions

Temperature: 80 °C

Procedure

To 4-bromo-1-(difluoromethoxy)-2-methylbenzene (2.36 g, 10.00 mmol) in toluene (50 mL) was added cis-2,6-dimethylpiperazine (5 g, 58.14 mmol), Pd(OAc)2 (120 mg, 0.53 mmol), BINAP (380 mg, 0.61 mmol), and t-BuOK (2.2 g, 19.64 mmol). The resulting solution was stirred for 4 hours at 80° C. The solution was cooled to room temperature and washed with H2O (2×50 mL), dried over Na2SO4, concentrated, and purified by silica gel column chromatography (10:1 CH2Cl2/MeOH) to give 1.1 g (41%) of 1-(4-(difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine.

Workup

temperatureThe solution was cooled to room temperature
washwashed with H2O (2×50 mL)
dry with materialdried over Na2SO4
concentrationconcentrated
custompurified by silica gel column chromatography (10:1 CH2Cl2/MeOH)

Sources & evidence

ORD record: ord-5c3bc382159b40b384bb156f94513bb8
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07517884B2

Reaction notes

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