Potassium Hydroxide → HCID 25010404, compound

HRID 607063Notes

Reaction equation

HRID 607063 reaction equation
[F:1][C:2]([F:38])([F:37])[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]([F:26])[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31](Br)[CH:30]=[CH:29][C:28]=3[O:34][CH3:35])[C@H:14]2[CH3:36])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=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:38])([F:37])[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]([F:26])[CH:23]=[CH:22][C:21]=3[C:27]3[C:28]([O:34][CH3:35])=[CH:29][CH:30]=[C:31]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=4[CH3:39])[CH:32]=3)[C@H:14]2[CH3:36])[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 57704830(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5'-bromo-4-fluoro-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 25010404HCID 25010404, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5′-bromo-4-fluoro-2′-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (50 mg, 0.082 mmol), (2-methylphenyl) boronic acid (22 mg, 0.165 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (20 mg, 0.024 mmol), aqueous potassium hydroxide (55 μL, 3M, 0.165 mmol) and 1,4-dioxane (1 mL) were placed in a sealed tube and subjected to microwave irradiation at 140° C. for 20 minutes to complete the reaction. The crude reaction mixture was purified by preparative TLC on SiO2 (eluted with 20% Ethyl Acetate in hexanes) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-fluoro-6′-methoxy-2″-methyl-1,1′:3′,1″-terphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one as a colorless glass. LCMS calc.=617.18; found=618.16 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 7.84 (s, 1H), 7.68 (s, 1H), 7.62 (s, 1H), 7.36-7.32 (m, 1H), 7.30-7.22 (m, 4H), 7.22-7.18 (m, 1.5H), 7.18-7.14 (m, 0.5H), 7.14-7.11 (m, 1H), 7.11-7.05 (m, 1H), 7.02 (t, J=8.0 Hz, 1H), 5.58 (d, J=8.5 Hz, 0.55H), 5.28 (d, J=8 Hz, 0.45H), 4.90 (d, J=3.5 Hz, 0.45H), 4.09 (d, J=15.5 Hz, 0.45H), 3.88 (d, J=16.5 Hz, 0.55H), 3.844, 3.838 (s, 3H), 3.82-3.75 (m, 1H), 2.32, 2.56 (s, 3H), 0.52 (d, J=6.5 Hz, 1.35H), 0.38 (d, J=6.5 Hz, 1.65H).

Workup

  1. customirradiation at 140° C. for 20 minutes
  2. customthe reaction
  3. customThe crude reaction mixture
  4. customwas purified by preparative TLC on SiO2 (eluted with 20% Ethyl Acetate in hexanes)

Sources & evidence

ORD record
ord-9e88ebc3ad224f98b0a51bdf718818e2
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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