Potassium Carbonate → methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-chloro-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 2093196Notes

Reaction equation

HRID 2093196 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2I)[O:9][C:8]1=[O:24].[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][C:44]([C:47]([O:49][CH3:50])=[O:48])=[CH:43][C:42]=2[CH3:51])=[CH:37][C:36]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>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].C(O)C>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[C:40]2[CH:39]=[C:38]([C:41]3[CH:46]=[CH:45][C:44]([C:47]([O:49][CH3:50])=[O:48])=[CH:43][C:42]=3[CH3:51])[CH:37]=[CH:36][C:35]=2[Cl:34])[O:9][C:8]1=[O:24]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57704833Methyl 4'-chloro-2-methyl-3'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylateHCID 59135170(4R,5R)-3-[3,5-Bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86630546methyl 2''-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4'-chloro-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolvent

Procedure

(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (103 mg, 0.172 mmol, in 515 μL toluene), methyl 4′-chloro-2-methyl-3′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (100 mg, 0.259 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (14 mg, 10%), aqueous potassium carbonate (344 μL, 2M, 0.688 mmol), and ethanol (2 mL) were sealed in a microwave vessel. The reaction mixture was irradiated by microwave at 140° C. for 45 minutes. LC/MS analysis indicated complete consumption of starting material. Crude material was purified by SiO2 (Prep-TLC 30% EtOAc/hex) to afford a yellow residue. The residue was further purified by a preparative reverse phase HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting w/ a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture affording methyl 2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-chloro-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. LCMS calc.=729.13; found=730.14 (M+1)+.

Workup

  1. customThe reaction mixture was irradiated by microwave at 140° C. for 45 minutes
  2. customconsumption of starting material
  3. customCrude material was purified by SiO2 (Prep-TLC 30% EtOAc/hex)
  4. customto afford a yellow residue
  5. customThe residue was further purified by a preparative reverse phase HPLC (Kromasil 100-5C18, 100×21.1 mm)
  6. washeluting w/ a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture

Sources & evidence

ORD record
ord-1b90c18288c54c588ba8c75056a7ba01
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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