Potassium Phosphate, Tribasic → methyl 2,2-dimethyl-3-({4-methyl-6'-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3'-bipyridin-6-yl}oxy)propanoate

HRID 623887Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=2)=[N:6][CH:7]=1.[CH3:25][C:26]([CH3:49])([CH2:31][O:32][C:33]1[CH:38]=[C:37]([CH3:39])[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=1)[C:27]([O:29][CH3:30])=[O:28].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)(O)[O-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.O1CCCC1>[CH3:25][C:26]([CH3:49])([CH2:31][O:32][C:33]1[N:34]=[CH:35][C:36]([C:2]2[CH:7]=[N:6][C:5]([C:8]3[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=3)=[CH:4][CH:3]=2)=[C:37]([CH3:39])[CH:38]=1)[C:27]([O:29][CH3:30])=[O:28]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture in which tetrahydrofuran (6 mL) was added to 5-bromo-2-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine (542 mg), methyl 2,2-dimethyl-3-{[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridin-2-yl]oxy}propanoate (372 mg), potassium phosphate (302 mg), palladium acetate (8 mg) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (29 mg) was stirred under nitrogen atmosphere at 50° C. for 6 hours. After cooling the mixture to room temperature, a saturated aqueous sodium bicarbonate solution, water and ethyl acetate were added to the mixture and the resulting mixture was stirred. The organic layer was separated, washed with a saturated brine, and the residue obtained by concentrating under reduced pressure was purified by silica gel column chromatography (n-hexane:ethyl acetate=90:10 to 60:40) to obtain methyl 2,2-dimethyl-3-({4-methyl-6′-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]-3,3′-bipyridin-6-yl}oxy)propanoate (100 mg).

Workup

temperatureAfter cooling the mixture to room temperature
stirringthe resulting mixture was stirred
customThe organic layer was separated
washwashed with a saturated brine
customthe residue obtained
concentrationby concentrating under reduced pressure
customwas purified by silica gel column chromatography (n-hexane:ethyl acetate=90:10 to 60:40)

Sources & evidence

ORD record: ord-409ec658ed14457b8939532a9d3c2e7d
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09302996B2

Reaction notes

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