1,2-Dichloroethane → N-[(4aR,8aS)-8a-(2,4-difluorophenyl)-6-oxo-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 590601Notes

Reaction equation

HRID 590601 reaction equation
C(OC=[C:6]1[O:24][CH2:23][C@:9]2([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=3[F:32])[N:10]=[C:11]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[S:12][CH2:13][C@@H:8]2[CH2:7]1)(=O)C.I([O-])(=O)(=O)=[O:34].[Na+].ClCCCl.O>C(#N)C.[Ru](Cl)(Cl)Cl>[F:32][C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[C@:9]12[CH2:23][O:24][C:6](=[O:34])[CH2:7][C@H:8]1[CH2:13][S:12][C:11]([NH:14][C:15](=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[N:10]2

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 962WaterHCID 23667635Sodium periodateHCID 123599379[(4aR,8aS)-2-(benzoylamino)-8a-(2,4-difluorophenyl)-4a,5,8,8a-tetrahydropyrano[3,4-d][1,3]thiazin-6(4H)-ylidene]methyl acetate

Product 1

HCID 89889294N-[(4aR,8aS)-8a-(2,4-difluorophenyl)-6-oxo-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Reagents, catalysts & solvents 2

HCID 61850Ruthenium trichlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of [(4aR,8aS)-2-(benzoylamino)-8a-(2,4-difluorophenyl)-4a,5,8,8a-tetrahydropyrano[3,4-d][1,3]thiazin-6(4H)-ylidene]methyl acetate (C11) (430 mg, 0.938 mmol), ruthenium(III) chloride (5.8 mg, 28 μmol) and sodium periodate (98.5%, 407 mg, 1.87 mmol) in acetonitrile (0.5 mL) and a 1:1 mixture of 1,2-dichloroethane and water (5 mL) was stirred for 3 hours at room temperature, then allowed to stand for 18 hours without stirring. After dilution with saturated aqueous sodium thiosulfate solution (25 mL), the mixture was extracted with ethyl acetate (3×50 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 80% ethyl acetate in heptane) provided the product as a white solid. Yield: 237 mg, 0.589 mmol, 63%. LCMS m/z 403.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.99 (br d, J=8 Hz, 2H), 7.49-7.54 (m, 1H), 7.43 (br dd, J=8, 7 Hz, 2H), 7.32 (ddd, J=9.0, 9.0, 6.3 Hz, 1H), 6.81-6.93 (m, 2H), 4.85 (d, J=11.7 Hz, 1H), 4.24 (d, J=11.5 Hz, 1H), 3.35-3.44 (m, 1H), 2.87-2.97 (m, 2H), 2.80 (dd, half of ABX pattern, J=18.7, 7.5 Hz, 1H), 2.63 (dd, J=13.1, 3.1 Hz, 1H).

Workup

  1. waitto stand for 18 hours
  2. stirringwithout stirring
  3. extractionAfter dilution with saturated aqueous sodium thiosulfate solution (25 mL), the mixture was extracted with ethyl acetate (3×50 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cd931060cb3742838273a30584ea0e57
Source dataset
uspto-grants-2016_01
Patent number
US09233981B1

Reaction notes

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