Toluene → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(2'-chloro-5'-isopropyl-4-nitrobiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1994639Notes

Reaction equation

HRID 1994639 reaction equation
[F:1][C:2]([F:32])([F:31])[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]([N+:26]([O-:28])=[O:27])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:30])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1(C)C=CC=CC=1.[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([CH:47]([CH3:49])[CH3:48])=[CH:43][C:42]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[F:1][C:2]([F:32])([F:31])[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]([N+:26]([O-:28])=[O:27])[CH:23]=[CH:22][C:21]=3[C:42]3[CH:43]=[C:44]([CH:47]([CH3:49])[CH3:48])[CH:45]=[CH:46][C:41]=3[Cl:40])[C@H:14]2[CH3:30])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 57509290HCID 57509290, compoundHCID 86603442(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 11664390(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(2'-chloro-5'-isopropyl-4-nitrobiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one (950 mg, 1.80 mmol) in a toluene (5.2 mL): ethanol (2.6 mL): water (1.3 mL) mixture was added (2-chloro-5-isopropylphenyl) boronic acid (325 mg, 1.64 mmol), tetrakis(triphenylphosphine)palladium(0) (188 mg, 10 mol %) and sodium carbonate (346 mg, 3.26 mmol). The resulting mixture was heated in an 80° C. oil bath for 12 h. The reaction crude was evaporated into dryness. The resulting residue was taken up by a mixture of water and EtOAc. The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude product, which was purified by SiO2 (Biotage 40+S cartridge, EtOAc/hexane, gradient) to afford the titled compound. LC-MS: 601.19 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 1:1 mixture of rotamers δ 8.31-8.30 (m, 1H), 8.24-8.28 (m, 1H), 7.85-7.89 (m, 1H), 7.68-7.76 (m, 2H), 7.42-7.48 (m, 2H), 7.26-7.30 (m, 1H), 7.04-7.11 (m, 1H), 5.74 (d, J=7.8 Hz, 0.5H), 5.58 (d, J=8.0 Hz, 0.5H), 4.92 (d, J=15.8 Hz, 0.5H), 4.76 (d, J=16.2 Hz, 0.5H), 3.97-4.04 (m, 1.5H), 3.82 (dt, J=8.0, 6.6 Hz, 0.5H), 2.89-2.99 (m, 1H) 1.22-1.29 (m, 6H), 0.60 (d, J=6.4 Hz, 1.5H), 0.52 (d, J=6.6 Hz, 1.5H).

Workup

  1. customThe reaction crude
  2. customwas evaporated into dryness
  3. additionThe resulting residue was taken up by a mixture of water and EtOAc
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give the crude product, which
  7. customwas purified by SiO2 (Biotage 40+S cartridge, EtOAc/hexane, gradient)

Sources & evidence

ORD record
ord-d6f3ff62872641668386894e7050ca14
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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