Cesium carbonate → HCID 58109711, compound

HRID 2037498Notes

Reaction equation

HRID 2037498 reaction equation
[CH2:1]([C:4]1([CH:20]([CH3:22])[CH3:21])[O:9][C:8](=[O:10])[N:7]([CH: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:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1B(O)O.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([CH:20]([CH3:22])[CH3:21])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:27]3[CH:26]=[CH:25][C:24]([F:23])=[CH:29][C:28]=3[F:30])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343342,4-Difluorophenylboronic acidHCID 66856517HCID 66856517, compound

Product 1

HCID 58109711HCID 58109711, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-allyl-3-[1-(4-bromo-phenyl)-ethyl]-6-isopropyl-[1,3]oxazinan-2-one (200 mg, 0.55 mmol), 2,4-difluorophenylboronic acid (104 mg, 0.66 mmol), PdCl2(PPh3)2 (20 mg), aqueous Cs2CO3 solution (2 M, 2 mL) in 1,4-dioxane (8 mL) was heated to reflux for 2 h. The mixture was filtered, and the filtrate was extracted with EtOAc for 3 times. 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 6-allyl-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-isopropyl-1,3-oxazinan-2-one (160 mg, 73%). 1H NMR (CDCl3): 0.96 (m, 6H), 1.61 (m, 3H), 1.68-2.09 (m, 3H), 2.32-2.47 (m, 2H), 2.84 (m, 1H), 3.18 (m, 1H), 5.02-5.19 (m, 2H), 5.84 (m, 2H), 6.93 (m, 2H), 7.41 (m, 3H), 7.50 (m, 2H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. filtrationThe mixture was filtered
  4. extractionthe filtrate was extracted with EtOAc for 3 times
  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-54e0ea00e333477283b6c6927a350f93
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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