Imidazole → 6-Chloro-3,4-dihydro-2-[4-[2-(t-butyldiphenylsiloxy)ethyl]phenyl]-4-hydroxy-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxide

HRID 1489818Notes

Reaction equation

HRID 1489818 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([Cl:9])[S:6][C:5]=1[S:10]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][OH:22])=[CH:16][CH:15]=1)(=[O:12])=[O:11])(=[O:3])[CH3:2].N1C=CN=C1.[Si:28](Cl)([C:41]([CH3:44])([CH3:43])[CH3:42])([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1C=C[NH+]=CC=1.Br[Br-]Br.[BH4-].[Na+]>C1COCC1.O.CN(C=O)C>[Cl:9][C:7]1[S:6][C:5]2[S:10](=[O:12])(=[O:11])[N:13]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][O:22][Si:28]([C:41]([CH3:44])([CH3:43])[CH3:42])([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:16][CH:15]=3)[CH2:2][CH:1]([OH:3])[C:4]=2[CH:8]=1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 4311764Sodium borohydrideHCID 229019243-Acetyl-5-chloro-N-[4-(2-hydroxyethyl)phenyl]-thiophene-2-sulfonamide

Product 1

HCID 229019656-Chloro-3,4-dihydro-2-[4-[2-(t-butyldiphenylsiloxy)ethyl]phenyl]-4-hydroxy-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxideYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The product from Step B (11.5 g, 0.032 mol) was added to DMF (100 mL) containing imidazole (5.44 g, 0.08 mol) and t-butyldiphenylsilyl chloride (9.34 mL, 0.035 mol) and stirred at room temperature for 18 hr. The reaction mixture was evaporated to dryness and the residue was suspended in methylene chloride and filtered. The filtrate was concentrated and chromatographed (silica, methylene chloride) to provide a solid which was dissolved in THF (200 mL) and cooled to 5° C. A solution of pyridinium bromide perbromide (11.23 g, 0.035 mol) in THF (50 mL) was added dropwise and this mixture was stirred at 5° C. for 1 hr, at ambient temperature for 1 hr, and then evaporated to dryness. The residue was suspended in ethanol (150 mL) and cooled to 5° C. followed by the addition of sodium borohydride (3.59 g, 95 mmol). The reaction mixture was maintained at room temperature for 1 hr and then heated at reflux temperature for 1.5 hr. Water was carefully added and the ethanol evaporated. The aqueous mixture was neutralized and extracted with ethyl acetate (2×200 mL). The combined extracts were dried (MgSO4) and evaporated to a residue which was purified by column chromatography (silica, 15% ethyl acetate/hexane) to provide an amber syrup (8.2 g, 44%).

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customchromatographed (silica, methylene chloride)
  5. customto provide a solid which
  6. temperaturecooled to 5° C
  7. stirringthis mixture was stirred at 5° C. for 1 hr, at ambient temperature for 1 hr
  8. customevaporated to dryness
  9. temperaturecooled to 5° C.
  10. temperatureThe reaction mixture was maintained at room temperature for 1 hr
  11. temperatureheated
  12. temperatureat reflux temperature for 1.5 hr
  13. customthe ethanol evaporated
  14. extractionextracted with ethyl acetate (2×200 mL)
  15. dry with materialThe combined extracts were dried (MgSO4)
  16. customevaporated to a residue which
  17. customwas purified by column chromatography (silica, 15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-6088c33bb76a4c9ba278bbb14562d5ce
Source dataset
uspto-grants-1997_10
Patent number
US05679670

Reaction notes

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