Potassium Hydroxide → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[2'-chloro-4'-fluoro-5'-isopropyl-4-(methylthio)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 1994638Notes

Reaction equation

HRID 1994638 reaction equation
[F:1][C:2]([F:31])([F:30])[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]([S:26][CH3:27])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:29])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Cl:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([CH:40]([CH3:42])[CH3:41])=[CH:35][C:34]=1B(O)O.[OH-].[K+]>O1CCOCC1.Cl[Pd]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:1][C:2]([F:31])([F:30])[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]([S:26][CH3:27])[CH:23]=[CH:22][C:21]=3[C:34]3[CH:35]=[C:36]([CH:40]([CH3:42])[CH3:41])[C:37]([F:39])=[CH:38][C:33]=3[Cl:32])[C@H:14]2[CH3:29])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 59135210(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-bromo-5-(methylthio)benzyl]-4-methyl-1,3-oxazolidin-2-oneHCID 66716668(2-Chloro-4-fluoro-5-isopropylphenyl)boronic acid

Product 1

HCID 11685920(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[2'-chloro-4'-fluoro-5'-isopropyl-4-(methylthio)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-bromo-5-(methylthio)benzyl]-4-methyl-1,3-oxazolidin-2-one (60 mg, 0.114 mmol) in 1,4-dioxane (1 mL) was added (2-chloro-4-fluoro-5-isopropylphenyl)boronic acid (10 mg, 0.12 mmol), [1,1′-bis(diphenylphosphino) ferrocene] dichloropalladium (II) (28 mg, 30 mol %) and aqueous potassium hydroxide (95 μL, 3M, 2 eq.). The reaction mixture was purged with nitrogen and then sealed in a microwave vessel. The reaction vessel was subject to microwave irradiation at 150° C. for 30 min. Crude mixture was worked up with water and EtOAc. The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude product. This was purified by preparative TLC plate to afford the titled compound. LC-MS: 619.95 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 1:1 mixture of rotamers δ 7.83-7.88 (m, 1H), 7.72 (s, 1H) 7.68 (s, 1H), 7.30-7.35 (m, 1H), 7.24-7.29 (m, 1H), 7.11-7.19 (m, 2.5H), 7.04-7.07 (m, 0.5H), 5.62 (d, J=8.2 Hz, 0.5H), 5.24 (d, J=8.0 Hz, 0.5H), 4.87 (d, J=15.3 Hz, 0.5H), 4.70 (d, J=15.8 Hz, 0.5H), 3.79-3.98 (m, 2H), 3.18 (m, 1H), 2.55 (s, 1.5H), 2.54 (s, 1.5H), 1.20-1.29 (m, 6H), 0.53 (d, J=6.4 Hz, 1.5H), 0.47 (d, J=6.6 Hz, 1.5H).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed in a microwave vessel
  3. customirradiation at 150° C. for 30 min
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by preparative TLC plate

Sources & evidence

ORD record
ord-a054b9aa83cb4a2082dc51780e30975d
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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