Sodium Carbonate → methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 2093207Notes

Reaction equation

HRID 2093207 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:17]=[C:16](I)[C:15]([O:19][CH3:20])=[CH:14][C:13]=1[F:21].[F:22][C:23]([F:62])([F:61])[C:24]1[CH:25]=[C:26]([C@H:34]2[O:38][C:37](=[O:39])[N:36]([CH2:40][C:41]3[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][C:42]=3B3OC(C)(C)C(C)(C)O3)[C@H:35]2[CH3:60])[CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1.C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[F:62][C:23]([F:22])([F:61])[C:24]1[CH:25]=[C:26]([C@H:34]2[O:38][C:37](=[O:39])[N:36]([CH2:40][C:41]3[CH:46]=[C:45]([C:47]([F:48])([F:49])[F:50])[CH:44]=[CH:43][C:42]=3[C:16]3[CH:17]=[C:12]([C:3]4[CH:4]=[CH:5][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:7][C:2]=4[F:1])[C:13]([F:21])=[CH:14][C:15]=3[O:19][CH3:20])[C@H:35]2[CH3:60])[CH:27]=[C:28]([C:30]([F:31])([F:33])[F:32])[CH:29]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 57704843Methyl 2,2'-difluoro-5'-iodo-4'-methoxybiphenyl-4-carboxylateHCID 86630539HCID 86630539, compound2×

Product 1

HCID 57704789methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2,6'-difluoro-4'-methoxy-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

methyl 2,2′-difluoro-5′-iodo-4′-methoxybiphenyl-4-carboxylate (100 mg, 0.247 mmol), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (INTERMEDIATE 9, 179.2 mg, 0.30 mmol), sodium carbonate (247 μL, aq., 2M, 0.494 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (40 mg, 0.049 mmol) and 1,4-dioxane (2.1 ml) were heated in a 80° C. oil bath for 8 hours. Aliquot indicated formation of the desired product. Crude mixture was concentrated under reduced pressure. The pot residue was worked up w/H2O/EtOAc/Na2SO4/filtration followed by concentration to afford a dark oil. This oil was purified by a by reverse-phase prep-HPLC (Waters SunFire PrepC18 OBD 5μ, 30×100 mm) eluting w/a MeCN (0.05% TFA, v/v)/H2O (0.05% TFA, v/v) gradient mixture (10 to 100% in 12 min, hold 100% for 3 min) Related fractions were pooled & evaporated in vacuo to afford a dark oil. The oil was further purified by SiO2 (Prep-TLC 30% EtOAc/hex) to afford the title compound. LCMS (ESI) calc.=747.15; found=748.20 (M+1)+.

Sources & evidence

ORD record
ord-4e678e6eb1af442e9c8846aaa51569dc
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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