Hydrogen Peroxide → HCID 86650530, compound

HRID 1888141Notes

Reaction equation

HRID 1888141 reaction equation
C([C@H]1CCOC(=O)N1C(=O)[C@@H:16]([C@H:21]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C:22]1[CH:23]=[N:24][C:25]([Cl:28])=[CH:26][CH:27]=1)[CH2:17][CH2:18][C:19]#[CH:20])C1C=CC=CC=1.[O:38]1[CH2:42]CCC1.[OH:43]O.[OH-].[Na+]>O>[Si:30]([O:29][C@H:21]([C:22]1[CH:23]=[N:24][C:25]([Cl:28])=[CH:26][CH:27]=1)[C@@H:16]([CH2:17][CH2:18][C:19]#[CH:20])[C:42]([OH:38])=[O:43])([C:33]([CH3:34])([CH3:36])[CH3:35])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 86650529HCID 86650529, compound

Product 1

HCID 86650530HCID 86650530, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 37 g (70 mmol) of (4S)-4-benzyl-3-{(2R)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(6-chloropyridin-3-yl)methyl]hex-5-ynoyl}-1,3-oxazinan-2-one from Step C in 520 mL of a 3 to 1 mixture of anhydrous tetrahydrofuran to water at 0° C. under an atmosphere of nitrogen was added 30 mL (350 mmol) of a 35% aqueous hydrogen peroxide solution at a rate slow enough to keep the internal temperature below 3° C. Next, 140 mL (140 mmol) of a 1.0 M aqueous sodium hydroxide solution was added at a rate slow enough to keep the internal temperature of the reaction below 5° C. After complete addition the resulting mixture was stirred for 18 h at 0° C. then quenched with a solution of 350 mL (420 mmol) of a 1.2 M aqueous sodium sulfite solution at a rate slow enough to keep the internal temperature of the mixture below 15° C. All volatiles were removed in vacuo and the remaining aqueous phase was cooled to 0° C. and acidified with a 2.5 M aqueous hydrogen chloride solution until a pH of 3 was achieved. The aqueous phase was then extracted with ethyl acetate (3×200 mL) and the combined organics were washed with brine (10 ml), dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 15% ethyl acetate and 3% acetic acid in hexanes to afford the title compound as a white solid (16 g, 62%). LC-MS: m/z (ES) 368.2 (MH)+.

Workup

  1. customthe internal temperature below 3° C
  2. customthe internal temperature of the reaction below 5° C
  3. additionAfter complete addition the resulting mixture
  4. customthen quenched with a solution of 350 mL (420 mmol) of a 1.2 M aqueous sodium sulfite solution at a rate slow enough
  5. customthe internal temperature of the mixture below 15° C
  6. customAll volatiles were removed in vacuo
  7. temperaturethe remaining aqueous phase was cooled to 0° C.
  8. extractionThe aqueous phase was then extracted with ethyl acetate (3×200 mL)
  9. washthe combined organics were washed with brine (10 ml)
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customThe residue was purified by silica gel chromatography
  14. washeluting with 15% ethyl acetate and 3% acetic acid in hexanes

Sources & evidence

ORD record
ord-57c0f12ed0c5412a9700edcd2cb722bf
Source dataset
uspto-grants-2013_08
Patent number
US08501786B2

Reaction notes

Loading…