Sodium Hydroxide → (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 1191785Notes

Reaction equation

HRID 1191785 reaction equation
N[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]([N:16]3[CH2:21][CH2:20][C@@:19]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)([CH2:22][CH2:23][CH2:24][OH:25])[O:18][C:17]3=[O:33])[CH3:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.N([O-])=[O:35].[Na+].[OH-].[Na+]>OS(O)(=O)=O>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C@:19]2([CH2:22][CH2:23][CH2:24][OH:25])[O:18][C:17](=[O:33])[N:16]([C@H:14]([C:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:4]=[CH:3][C:2](=[O:35])[NH:7][CH:6]=4)=[CH:9][CH:10]=3)[CH3:15])[CH2:21][CH2:20]2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 23668193Sodium NitriteHCID 59635760(R)-3-((S)-1-(4-(6-aminopyridin-3-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one

Product 1

HCID 59635635(R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

(R)-3-((S)-1-(4-(6-aminopyridin-3-yl)phenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (400 mg, 0.88 mmol.) was dissolved in 3.5 M H2SO4 (10 mL), and 2 M NaNO2 (6 mL) was added at 0° C. The reaction mixture was stirred at rt for 20 min. The reaction mixture was then treated with aqueous NaOH solution (8%), and extracted with CH2Cl2. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated to give crude product, which was purified by preparative TLC to give (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (350 mg, 0.78 mmol). 1H NMR (CDCl3): δ=1.10-1.25 (m, 8H), 1.37 (m, 1H), 1.42-1.55 (m, 2H), 1.78-1.93 (m, 2H), 2.10-2.38 (m, 2H), 2.87 (m, 2H), 3.52-3.58 (m, 1H), 3.31-3.97 (m, 1H), 4.12-4.19 (m, 1H), 5.53-5.63 (m, 1H), 6.85-7.15 (m, 3H), 7.35-7.55 (m, 1H), 7.75-7.89 (m, 1H), 8.10-8.12 (m, 1H).

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customto give crude product, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-9e4591c54a1e4157985c1dbbdb442290
Source dataset
uspto-grants-2014_03
Patent number
US08680093B2

Reaction notes

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