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

HRID 2093212Notes

Reaction equation

HRID 2093212 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5](I)=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=1[CH3:20].[F:21][C:22]([F:61])([F:60])[C:23]1[CH:24]=[C:25]([C@H:33]2[O:37][C:36](=[O:38])[N:35]([CH2:39][C:40]3[CH:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[CH:42][C:41]=3B3OC(C)(C)C(C)(C)O3)[C@H:34]2[CH3:59])[CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1.C.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.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]>[F:61][C:22]([F:21])([F:60])[C:23]1[CH:24]=[C:25]([C@H:33]2[O:37][C:36](=[O:38])[N:35]([CH2:39][C:40]3[CH:45]=[C:44]([C:46]([F:47])([F:48])[F:49])[CH:43]=[CH:42][C:41]=3[C:5]3[CH:4]=[C:3]([C:10]4[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=4[CH3:20])[C:2]([F:1])=[CH:7][C:6]=3[F:8])[C@H:34]2[CH3:59])[CH:26]=[C:27]([C:29]([F:30])([F:32])[F:31])[CH:28]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 57704766Methyl 2',4'-difluoro-5'-iodo-2-methylbiphenyl-4-carboxylateHCID 86630539HCID 86630539, compound2×

Product 1

HCID 57704834Methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)-phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4',6'-difluoro-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

methyl 2′,4′-difluoro-5′-iodo-2-methylbiphenyl-4-carboxylate (100 mg, 0.26 mmol, dissolved in 1 mL ethanol), (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, 185 mg, 0.31 mmol, dissolved in 2.2 mL 1,4-dioxane), sodium carbonate (258 μL, aq., 2M, 0.516 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (42 mg, 0.05 mmol) were heated in an 80° C. oil bath for 2 hours. LCMS trace of reaction aliquot indicated completion of reaction. Reaction crude was dried/Na2SO4 and then deposited on 2 prep-TLC plates (SiO2). The plates were developed by a 20% EtOAc/hexanes mixture to afford a clear glass. The glass was further purified by reverse-phase prep-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. Corresponding fractions were pooled & evaporated in vacuo to afford a colorless glass. This glass was dissolved in DCM and washed with water. Organic extracts were combined, dried/Na2SO4, filtered and evaporated to afford the title compound. LCMS (ESI) calc.=731.15; found=732.06 (M+1)+.

Workup

  1. customLCMS trace of reaction
  2. customcompletion of reaction
  3. customReaction crude
  4. dry with materialwas dried/Na2SO4
  5. customto afford a clear glass
  6. customThe glass was further purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  7. washeluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
  8. customevaporated in vacuo
  9. customto afford a colorless glass
  10. washwashed with water
  11. dry with materialdried/Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-f3a911b015574f2a927f3428f244705e
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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