Potassium Phosphate, Tribasic → 4-{4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalen-1-yl}-pyrazole-1-carboxylic acid tert-butyl ester

HRID 388370Notes

Reaction equation

HRID 388370 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([C:41]2[CH2:45][C:44]([C:50]3[CH:55]=[C:54]([Cl:56])[CH:53]=[C:52]([Cl:57])[CH:51]=3)([C:46]([F:49])([F:48])[F:47])[O:43][N:42]=2)=[CH:33][CH:32]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34]([C:41]3[CH2:45][C:44]([C:50]4[CH:51]=[C:52]([Cl:57])[CH:53]=[C:54]([Cl:56])[CH:55]=4)([C:46]([F:49])([F:47])[F:48])[O:43][N:42]=3)=[CH:33][CH:32]=2)[CH:10]=[N:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 866452773-(4-Bromo-1-naphthalenyl)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazole

Product 1

HCID 674362084-{4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalen-1-yl}-pyrazole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

1-Tert-butoxycarbonyl-4-1H-pyrazoleboronic acid pinacol ester (126 mg), Tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3 (7 mg)], K3PO4 (185 mg) and 2-dicyclohexylphosphinno-2′,6′-dimethoxybiphenyl (12 mg) are added to a solution of 3-(4-bromo-naphthalen-1-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (140 mg) in dry toluene (2.4 ml). After 16 hours at 75° C. the reaction is cooled down to room temperature and filtrated. The filtrate is concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield 4-{4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalen-1-yl}-pyrazole-1-carboxylic acid tert-butyl ester (compound 1.10, Table 1) as a colorless oil.

Workup

  1. filtrationfiltrated
  2. concentrationThe filtrate is concentrated in vacuo
  3. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-943387d0212c431fa87db4d94dfbf64d
Source dataset
uspto-grants-2013_02
Patent number
US08377942B2

Reaction notes

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