Water → HCID 58109492, compound

HRID 2037549Notes

Reaction equation

HRID 2037549 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][C@@:5]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:10][C:9](=[O:11])[N:8]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]=[CH2:21])=[CH:16][CH:15]=2)[CH3:13])[CH2:7][CH2:6]1.[OH2:28].O=O>CN(C=O)C.CCOC(C)=O.[Cu]Cl.[Pd](Cl)Cl>[C:20]([C:17]1[CH:16]=[CH:15][C:14]([C@@H:12]([N:8]2[CH2:7][CH2:6][C@:5]([CH2:4][CH2:3][CH2:2][OH:1])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:10][C:9]2=[O:11])[CH3:13])=[CH:19][CH:18]=1)(=[O:28])[CH3:21]

Participants

8

Reactant 3

HCID 962WaterHCID 977OxygenHCID 58109276HCID 58109276, compound

Product 1

HCID 58109492HCID 58109492, compoundYield 52%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 62652Cuprous chlorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A round-bottom flask was charged with copper(I) chloride (49 mg, 0.5 mmol), and a solution of (R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-vinylphenyl)ethyl)-1,3-oxazinan-2-one (80 mg, 0.2 mmol) in DMF (3 mL) was added, followed by H2O (0.5 mL) and palladium(II) chloride (18 mg, 0.1 mmol). The reaction mixture was vigorously stirred under a balloon of oxygen at rt overnight. The reaction was diluted with EtOAc (5 mL), and filtered. The filtrate was separated, and the aqueous layer 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 afford (R)-3-((S)-1-(4-acetylphenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one (40 mg, 52%). 1H NMR (CDCl3): 1.34 (m, 1H), 1.49 (m, 3H), 1.68 (m, 1H), 1.92 (m, 2H), 2.11-2.27 (m, 3H), 2.46 (s, 3H), 2.84 (m, 2H), 3.51 (m, 2H), 5.64 (m, 1H), 6.86 (m, 2H), 7.26 (m, 6H), 7.51 (m, 2H).

Workup

  1. filtrationfiltered
  2. customThe filtrate was separated
  3. extractionthe aqueous layer was extracted with EtOAc (3×)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-5834251d569f4194aa7e8e94f1ccaaef
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

Loading…