Ethyl Acetate → 6-(3-hydroxypropyl)-6-isopropyl-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 1096357Notes

Reaction equation

HRID 1096357 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][C:5]1([CH:29]([CH3:31])[CH3:30])OC(=O)[N:8]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[CH:16][CH:15]=2)[CH3:13])[CH2:7][CH2:6]1.CC(C)(C[C@@]1(C2C=CC=CC=2)OC(=O)N([C@H](C2C=CC([C:52]3[CH:57]=[CH:56][NH:55][C:54](=[O:58])[CH:53]=3)=CC=2)C)CC1)C#N.[C:66]([O-:69])([O-])=[O:67].[Cs+].[Cs+].[CH3:72]COC(C)=O>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.O>[OH:1][CH2:2][CH2:3][CH2:4][C:5]1([CH:29]([CH3:30])[CH3:31])[O:69][C:66](=[O:67])[N:8]([C@H:12]([C:14]2[CH:15]=[CH:16][C:17]([C:52]3[CH:57]=[CH:56][N:55]([CH3:72])[C:54](=[O:58])[CH:53]=3)=[CH:18][CH:19]=2)[CH3:13])[CH2:7][CH2:6]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 596357032,2-dimethyl-3-((R)-2-oxo-3-((S)-1-(4-(2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-6-yl)propanenitrileHCID 596357376-(3-hydroxypropyl)-6-isopropyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 667357286-(3-hydroxypropyl)-6-isopropyl-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-(3-hydroxypropyl)-6-isopropyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (40 mg, 0.092 mmol), 4-iodo-1-methylpyridin-2(1′-O-one (20 mg, 0.085 mmol), Pd(PPh3)2Cl2 (6 mg, 0.0085 mmol), and Cs2CO3 (2 N, 0.425 mL, 0.85 mmol) in 1,4-dioxane (2 mL) was refluxed for 3 h under N2. The reaction mixture was treated with EtOAc (20 mL) and water (20 mL), and the organic layer was dried and concentrated in vacuo. The residue was purified by preparative HPLC to give two isomers.

Workup

  1. temperaturewas refluxed for 3 h under N2
  2. customthe organic layer was dried
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by preparative HPLC
  5. customto give two isomers

Sources & evidence

ORD record
ord-25938a9c1cf644c08c4ee786abce8219
Source dataset
uspto-grants-2012_03
Patent number
US08138178B2

Reaction notes

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