Potassium Hydroxide → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6'-fluoro-2''-methyl-4-(trifluoromethyl)-1,1':3',1''-terphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 2093166Notes

Reaction equation

HRID 2093166 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34](Br)[CH:33]=[CH:32][C:31]=3[F:37])[C@H:14]2[CH3:38])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1B(O)O.[OH-].[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].O1CCOCC1>[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[C:31]([F:37])=[CH:32][CH:33]=[C:34]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[CH3:41])[CH:35]=3)[C@H:14]2[CH3:38])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 27332672-Methylphenyl boronic acidHCID 57704841(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-bromo-2'-fluoro-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 57704772(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6'-fluoro-2''-methyl-4-(trifluoromethyl)-1,1':3',1''-terphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-bromo-2′-fluoro-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (79 mg, 0.123 mmol), (2-methylphenyl) boronic acid (25 mg, 0.182 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (10 mg, 0.0122 mmol), aqueous potassium hydroxide (82 μL, 3M, 0.246 mmol) and 1,4-dioxane (1 mL) were placed in a sealed tube and subjected to microwave irradiation at 140° C. for 15 minutes to complete the reaction. The crude reaction mixture was purified by preparative TLC on SiO2 (eluted with 30% Ethyl Acetate in hexanes) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6′-fluoro-2″-methyl-4-(trifluoromethyl)-1,1′:3′,1″-terphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one as a ckcar glass. LCMS calc.=655.16; found=656.11 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 7.86 (s, 1H), 7.73 (s, 1H), 7.72-7.66 (m, 2H), 7.48 (d, J=8 Hz, 1H), 7.41-7.36 (m, 1H), 7.29-7.23 (m, 4H), 7.19-7.23 (m, 3H), 5.56 (br s, 1H), 4.96 (br s, 1H), 4.13 (br d, J=46.5 Hz, 1H), 3.83 (br d, J=43.5 Hz, 1H), 2.29 (s, 3H), 0.56, 0.51 (br s, 3H).

Workup

  1. customirradiation at 140° C. for 15 minutes
  2. customthe reaction
  3. customThe crude reaction mixture
  4. customwas purified by preparative TLC on SiO2 (eluted with 30% Ethyl Acetate in hexanes)

Sources & evidence

ORD record
ord-11882d4974c243319368cacecee5e00c
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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