Nitrogen → HCID 11606755, compound

HRID 1028657Notes

Reaction equation

HRID 1028657 reaction equation
[F:1][C:2]([F:30])([F:29])[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]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3Cl)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F:31][C:32]1[C:37]([CH:38]([CH3:40])[CH3:39])=[CH:36][C:35](B(O)O)=[C:34]([O:44][CH3:45])[CH:33]=1.[OH-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.N#N>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCCCCC>[F:1][C:2]([F:30])([F:29])[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]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[C:35]3[CH:36]=[C:37]([CH:38]([CH3:40])[CH3:39])[C:32]([F:31])=[CH:33][C:34]=3[O:44][CH3:45])[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 14797Potassium HydroxideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 53363739(4-Fluoro-5-isopropyl-2-methoxyphenyl)boronic acidHCID 59135207(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-chloro-4-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 11606755HCID 11606755, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-chloro-4-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one (100 mg, 0.22 mmol) in 1,4-dioxane (1 mL) was added (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (55.8 mg, 0.26 mmol), palladium(II) acetate (10 mg, 20 mol %), potassium hydroxide aqueous solution (147 μL, 3M, 2 eq.) and tri-tert-butylphosphine (13.4 mg, 0.066 mmol, 30 mol % as a 10% w/w hexane solution). The resulting reaction mixture was N2 purged and sealed in a microwave vessel. The vessel was subject to microwave irradiation at 140° C. for 40 min. LC-MS indicated the formation of desired product. It was quenched with water (50 mL). Volatiles were evaporated. The resulting mixture was extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo to an oil. The titled compound was obtained after two purifications with silica gel and one reversed phase prep-HPLC. LC-MS: 588.25 (M+1)+.

Workup

  1. customThe resulting reaction mixture
  2. custompurged
  3. customsealed in a microwave vessel
  4. customirradiation at 140° C. for 40 min
  5. customIt was quenched with water (50 mL)
  6. customVolatiles were evaporated
  7. extractionThe resulting mixture was extracted with EtOAc
  8. dry with materialThe combined extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to an oil

Sources & evidence

ORD record
ord-daeae77443f842459abcd742bb3a76b5
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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