Cesium carbonate → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(3-methylpiperidin-1-yl)-5-nitrobenzyl]-1,3-oxazolidin-2-one

HRID 505318Notes

Reaction equation

HRID 505318 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.[CH3:33][CH:34]1[CH2:39][CH2:38][CH2:37][NH:36][CH2:35]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[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[N:36]3[CH2:37][CH2:38][CH2:39][CH:34]([CH3:33])[CH2:35]3)[C@H:14]2[CH3:30])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 790813-MethylpiperidineHCID 634876Binap, (A+-)-HCID 86603442(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 24896058(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(3-methylpiperidin-1-yl)-5-nitrobenzyl]-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one (42 mg, 0.083 mmol), 3-methylpiperidine (13 mg, 0.126 mmol), palladium(II) acetate (1.0 mg, 5%), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (2-6 mg, 7.5%), cesium carbonate (55 mg, 0.17 mmol) and THF (1 mL) were sealed in a microwave vessel. The reaction mixture was irradiated by microwave at 150° C. for 1 hour. Reaction crude was purified by SiO2 to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(3-methylpiperidin-1-yl)-5-nitrobenzyl]-1,3-oxazolidin-2-one. LCMS calc.=546.17; found=546.23 (M+1)+. 1H NMR signals are doubled because of atropoisomerism 1H NMR (CDCl3, 500 MHz) δ 8.22 (d, J=2.5 Hz, 1H), 8.16 (d, J=3 Hz, 0.5H), 8.14 (d, J=2.5 Hz, 0.5H), 7.89 (s, 1H), 7.78 (s, 2H), 7.14 (d, J=4 Hz, 0.5H), 7.12 (d, J=4.0 Hz, 0.5H), 5.76 (d, J=8 Hz, 1H), 4.84 (d, J=4.5 Hz, 0.5H), 4.81 (d, J=4.5 Hz, 0.5H), 4.40 (d, J=3.5 Hz, 0.5H), 4.36 (d, J=3.5 Hz, 0.5H), 3.87-3.83 (m, 1H), 7.14 (s, 1H), 3.09 (s, 2H), 3.02 (d, J=12.5 Hz, 1H), 2.84 (t, J=10 Hz, 1H), 2.60 (t, J=12.5 Hz, 1H), 2.54 (t, J=11 Hz, 0.5H), 2.33 (t, J=11 Hz, 1H), 1.16-1.07 (m, 1H), 0.96 (d, J=6.5 Hz, 0.5H), 0.94 (d, J=6.5 Hz, 1.5H), 0.70 (s, 1.5H), 0.69 (s, 1.5H).

Workup

  1. customThe reaction mixture was irradiated by microwave at 150° C. for 1 hour
  2. customReaction crude
  3. customwas purified by SiO2

Sources & evidence

ORD record
ord-ff9ebe6e92e94d80a8435e9234c0715f
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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