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

HRID 607113Notes

Reaction equation

HRID 607113 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5](I)=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[C:13]([CH3:21])[CH:12]=1.[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]>[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:5]3[CH:4]=[C:3]([C:11]4[CH:16]=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[C:13]([CH3:21])[CH:12]=4)[C:2]([F:1])=[CH:7][C:6]=3[O:8][CH3:9])[C@H:35]2[CH3:60])[CH:27]=[C:28]([C:30]([F:31])([F:33])[F:32])[CH:29]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 57704857Methyl 2'-fluoro-5'-iodo-4'-methoxy-3-methylbiphenyl-4-carboxylateHCID 86630539HCID 86630539, compound4×

Product 1

HCID 57704852Methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6'-fluoro-4'-methoxy-3-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Procedure

methyl 2′-fluoro-5′-iodo-4′-methoxy-3-methylbiphenyl-4-carboxylate (135 mg, 0.337 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, 403 mg, 0.675 mmol, dissolved in 4.75 mL 1,4-dioxane), sodium carbonate (337 μL, aq., 2M, 0.674 mmol) and 1,1′-bis(diphenylphosphino) ferrocene-palladium dichloride dichloromethane adduct (55 mg, 0.07 mmol) were heated in an 80° C. oil bath for 2 hours then allowed to cooled to ambient overnight. Added additional (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, 200 mg, 0.335 mmol, dissolved in 2.35 mL 1,4-dioxane) and resumed heating for 2 more hours. Reaction aliquot indicated the presence of M+23 (LCMS). Crude mixture was cooled, dried/Na2SO4 and deposited on prep-TLC plates (SiO2). The plates were developed by a 30% DCM/hex mixture to afford a green oil of 350 mg. The green oil was further purified by prep-TLC (SiO2, 30% DCM/hexanes) to afford a green glass. The green oil/glass was further purified by prep-TLC (SiO2, 20% EtOAc/hexanes) to afford the title compound. LCMS (ESI) calc.=743.17; found=744 (M+1)+.

Workup

  1. temperatureto cooled to ambient overnight
  2. temperatureresumed heating for 2 more hours
  3. customReaction
  4. temperatureCrude mixture was cooled
  5. dry with materialdried/Na2SO4
  6. customto afford a green oil of 350 mg
  7. customThe green oil was further purified by prep-TLC (SiO2, 30% DCM/hexanes)
  8. customto afford a green glass
  9. customThe green oil/glass was further purified by prep-TLC (SiO2, 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-245d54e236fa45889859f2367febc7ff
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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