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

HRID 505317Notes

Reaction equation

HRID 505317 reaction equation
[F:1][C:2]([F:33])([F:32])[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]=3I)[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:34][C:35]1([CH3:41])[CH2:40][CH2:39][CH2:38][NH:37][CH2:36]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O1CCOCC1>[F:1][C:2]([F:33])([F:32])[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[N:37]3[CH2:38][CH2:39][CH2:40][C:35]([CH3:41])([CH3:34])[CH2:36]3)[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 709423,3-DimethylpiperidineHCID 53363742(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 24896011(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(3,3-dimethylpiperidin-1-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (500 mg, 0.837 mmol), 3,3-dimethylpiperidine (142.5 mg, 1.26 mmol), Bis(tri-t-butylphosphine)palladium (0) (43 mg, 0.084 mmol), cesium carbonate (685 mg, 2.10 mmol) and 1,4-dioxane (5 mL) were sealed in a microwave vessel. The reaction mixture was irradiated by microwave at 170° C. for 30 minutes. Reaction crude was purified by SiO2 to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(3,3-dimethylpiperidin-1-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=582.19; found=583.44 (M+1)+. 1H NMR signals are doubled because of atropoisomerism 1H NMR (CDCl3, 500 MHz) δ 7.88 (s, 1H), 7.77 (s, 2H), 7.58 (s, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H), 5.72 (d, J=8.0 Hz, 1H), 4.76 (d, J=16 Hz, 1H), 4.57 (d, J=15.5 Hz, 1H), 3.94-3.87 (m, 1H), 2.84 (br s, 1H), 2.68 (br s, 1H), 2.63 (d, J=11 Hz, 1H), 2.52 (d, J=11 Hz, 1H), 1.81 (br s, 1H), 1.71 (br s, 1H), 1.38 (br s, 2H), 1.06 (s, 3H), 0.99 (s, 3H), 0.67, 0.66 (s, 3H).

Workup

  1. customThe reaction mixture was irradiated by microwave at 170° C. for 30 minutes
  2. customReaction crude
  3. customwas purified by SiO2

Sources & evidence

ORD record
ord-5be4bd632655450f8bcb7ad99c753f2a
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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