2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → methyl (5R)-3-[4-(1,1-dioxido-2,3-dihydro-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxylate

HRID 896162Notes

Reaction equation

HRID 896162 reaction equation
[O:1]=[S:2]1(=[O:26])[CH2:7][CH2:6][N:5]([C:8]2[C:13]([F:14])=[CH:12][C:11]([N:15]3[CH2:19][C@H:18]([C:20]([O:22][CH3:23])=[O:21])[O:17][C:16]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.[O-]S([O-])=O.[Na+].[Na+]>O1CCOCC1.O>[O:26]=[S:2]1(=[O:1])[CH:3]=[CH:4][N:5]([C:8]2[C:13]([F:14])=[CH:12][C:11]([N:15]3[CH2:19][C@H:18]([C:20]([O:22][CH3:23])=[O:21])[O:17][C:16]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:6][CH2:7]1

Participants

6

Reactant 3

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 24437Sodium SulfiteHCID 68489310methyl (5R)-3-[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxylate

Product 1

HCID 68490087methyl (5R)-3-[4-(1,1-dioxido-2,3-dihydro-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxylateYield 38.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl (5R)-3-[4-(1,1-dioxidothiomorpholin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxylate (Step 2, 0.73 g, 1.87 mmol) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (1.27 g, 5.6 mmol) in dioxane (9 mL) is heated to 100° C. for two days. The solution is cooled and treated with 20 mL of 10% aqueous Na2SO3 and stirred for 30 minutes. The solution is then diluted with water and extracted three times with ethyl acetate. The combined organic phases are washed with satd NaHCO3 and saline and dried (MgSO4), filtered and concentrated. The crude residue is purified by column chromatography (0→5% ethyl ether-dichloromethane) to provide the title compound (0.28 g, 38%); 1H NMR (300 MHz, CDCl3): δ 3.31-3.35 (m, 2H), 3.89 (s, 3H), 4.00-4.15 (m, 3H), 4.25 (t, 1H), 5.11 (m, 1H), 5.45 (d, 1H), 6.54 (d, 1H), 7.29 (d, 2H).

Workup

  1. temperatureThe solution is cooled
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic phases are washed with satd NaHCO3 and saline
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue is purified by column chromatography (0→5% ethyl ether-dichloromethane)

Sources & evidence

ORD record
ord-d5c438620c7943d2a01cf6eff17ba64b
Source dataset
uspto-grants-2005_07
Patent number
US06919329B2

Reaction notes

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