Potassium Carbonate → (R)-1-[4-(2'-Difluoromethyl-biphenyl-3-yl)-piperazin-1-yl]-2-hydroxy-4-methyl-pentan-1-one

HRID 645461Notes

Reaction equation

[F:1][CH:2]([F:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B1OC(C)(C)C(C)(C)O1.Cl[C:20]1[CH:21]=[C:22]([N:26]2[CH2:31][CH2:30][N:29]([C:32](=[O:39])[CH:33]([OH:38])[CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:28][CH2:27]2)[CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>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.O.CC#N.CC#N.O>[F:18][CH:2]([F:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([N:26]2[CH2:27][CH2:28][N:29]([C:32](=[O:39])[C@H:33]([OH:38])[CH2:34][CH:35]([CH3:36])[CH3:37])[CH2:30][CH2:31]2)[CH:21]=1

Participants

Conditions

Temperature: 150 °C

Procedure

2-(2-Difluoromethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (34 mg, 0.11 mmol), 1-[4-(3-Chloro-phenyl)-piperazin-1-yl]-2-hydroxy -4-methyl-pentan-1-one (34 mg, 0.13 mmol), Pd(Ph3P)4 (1.3 mg, 10 μmol), K2CO3 (30.4 mg, 0.22 mmol), CH3CN (900 μL), and H2O (100 μL) were sealed in a microwave vessel and heated by microwave irradiation at 150° C. for 10 minutes. The reaction was filtered and purified by reverse phase HPLC (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)) to give 2. LCMS: m/z 403.7 (M+H)+ at 3.72 minutes (10% -99% CH3CN/H2O), (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

filtrationThe reaction was filtered
custompurified by reverse phase HPLC (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA))
customto give 2

Sources & evidence

ORD record: ord-aa89e2b9cff64693ada3630dff07c6c4
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07705002B2

Reaction notes

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