Methyl morpholine oxide → (-)-N-[[(5S)-3-(3,4-dihydro-2,2-dioxido-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 488370Notes

Reaction equation

HRID 488370 reaction equation
[CH2:1]1[C:6]2[CH:7]=[CH:8][C:9]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])=[CH:10][C:5]=2[CH2:4][CH2:3]S1.C[N+]1([O-])CCOCC1.[OH:30][S:31]([O-:33])=O.[Na+]>CC(C)=O.O.O=[Os](=O)(=O)=O>[O:30]=[S:31]1(=[O:33])[CH2:3][CH2:4][C:5]2[CH:10]=[C:9]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])[CH:8]=[CH:7][C:6]=2[CH2:1]1

Participants

6

Reactant 3

HCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 60054141(-)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide

Product 1

HCID 69734040(-)-N-[[(5S)-3-(3,4-dihydro-2,2-dioxido-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamideYield 86%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A solution of (−)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide (Example 10, 545 mg, 1.78 mmol) in acetone/H2O (3/1, 36 mL) under N2 is treated with N-methylmorpholine N-oxide (521 mg, 4.45 mmol) and OsO4 (2.5 wt % in tBuOH, 1.11 mL, 5 mol %), and the resulting mixture is stirred at ambient temperature for 18 hrs and is then cooled in an ice bath and treated with half-saturated aqueous NaHSO3 (50 mL). The mixture is extracted with CH2Cl2 (3×75 mL), and the combined organic phase is washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the crude product which is then chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (1/99-4/96). Those fractions with an Rf=0.39 by TLC (MeOH/CHCl3, 10/90) are pooled and concentrated and the product triturated with CH2Cl2/Et2O to give 517 mg (86%) of the title compound as a white solid, mp 177-178° C. MS (ESI+) for C15H18N2O5S m/z 339 (M+H)+; [α]25D=−23° (c 0.97, DMSO).

Workup

  1. temperatureis then cooled in an ice bath
  2. extractionThe mixture is extracted with CH2Cl2 (3×75 mL)
  3. washthe combined organic phase is washed with brine (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude product which
  7. customis then chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge
  8. washeluting with a gradient of MeOH/CH2Cl2 (1/99-4/96)
  9. concentrationconcentrated
  10. customthe product triturated with CH2Cl2/Et2O

Sources & evidence

ORD record
ord-7347c622c498414d80d2cf113cb2c2b7
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Reaction notes

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