Cesium carbonate → (R)-6-allyl-3-((S)-1-(4'-fluorobiphenyl-4-yl)ethyl)-6-phenyl-1,3-oxazinan-2-one

HRID 2193463Notes

Reaction equation

HRID 2193463 reaction equation
[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:30]3[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 59532360(R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one

Product 1

HCID 59532365(R)-6-allyl-3-((S)-1-(4'-fluorobiphenyl-4-yl)ethyl)-6-phenyl-1,3-oxazinan-2-oneYield 88%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (5.83 g, 15 mmol), 4-fluorophenylboronic acid (3 g, 22 mmol), PdCl2(PPh3)2 (1 g, 1.4 mmol), and aqueous Cs2CO3 solution (2 M, 8.0 mL) in 1,4-dioxane (50 mL) was heated to reflux for 2 h. The mixture was filtered, and the filtrate was extracted with EtOAc (3×). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude product, which was purified by preparative TLC to give (R)-6-allyl-3-((S)-1-(4′-fluorobiphenyl-4-yl)ethyl)-6-phenyl-1,3-oxazinan-2-one (5.3 g, 88%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. filtrationThe mixture was filtered
  4. extractionthe filtrate was extracted with EtOAc (3×)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-e3c804cfb3aa4688a467cd80e1084548
Source dataset
uspto-grants-2012_12
Patent number
US08329897B2

Reaction notes

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