Potassium Phosphate, Tribasic → 1-[2-Methyl-5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-phenyl]piperazine

HRID 2175073Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]([CH3:14])=[C:6]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=1.CC1(C)C(C)(C)OB([C:23]2[CH:32]=[CH:31][C:30]3[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]([CH3:36])([CH3:35])[C:25]=3[CH:24]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:14][C:5]1[CH:4]=[CH:3][C:2]([C:32]2[CH:23]=[CH:24][C:25]3[C:26]([CH3:36])([CH3:35])[CH2:27][CH2:28][C:29]([CH3:34])([CH3:33])[C:30]=3[CH:31]=2)=[CH:7][C:6]=1[N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1

Participants

Conditions

Temperature: 120 °C

Procedure

100 mg (0.48 mmol) of 1-(5-chloro-2-methylphenyl)piperazine and 300 mg (0.95 mmol) and of 4,4,5,5-tetramethyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,2-dioxaborolane are dissolved in 2 ml of THF, 302 mg (1.43 mmol) of potassium phosphate, 3 mg of palladium acetate and 11 mg of 2-dicylcohexylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphenyl are added. The reaction mixture is degassed a number of times and stirred at 120° C. under nitrogen atmosphere for 4 h, subsequently diluted with water and extracted three times with ethyl acetate. The combined organic phases are dried over Na2SO4 and evaporated. The crude product is purified by means of preparative HPLC and converted into the hydrochloride using methanolic HCl.

Workup

customThe reaction mixture is degassed a number of times
additionsubsequently diluted with water
extractionextracted three times with ethyl acetate
dry with materialThe combined organic phases are dried over Na2SO4
customevaporated
customThe crude product is purified by means of preparative HPLC

Sources & evidence

ORD record: ord-b4e70e2f73b948d19dc9b5b5a2fb871e
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062015B2

Reaction notes

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