Sodium Chloride → (4S)-6-Chloro-4-hydroxy-2-(2-methoxyethyl)-3,4-dihydro-1lambda~6~-thieno[3,2-e][1,2]thiazine-1,1(2H)-dione

HRID 2225472Notes

Reaction equation

HRID 2225472 reaction equation
[Cl:1][C:2]1[S:10][C:9]2[S:8](=[O:12])(=[O:11])[NH:7][CH2:6][C@@H:5]([OH:13])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][CH2:22][O:23][CH3:24].[Cl-].[Na+]>CS(C)=O>[Cl:1][C:2]1[S:10][C:9]2[S:8](=[O:11])(=[O:12])[N:7]([CH2:21][CH2:22][O:23][CH3:24])[CH2:6][C@@H:5]([OH:13])[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl ether3×HCID 11746721(4S)-6-chloro-1,1-dioxo-3,4-dihydro-2H-thieno(3,2-e)thiazin-4-ol

Product 1

HCID 15294529(4S)-6-Chloro-4-hydroxy-2-(2-methoxyethyl)-3,4-dihydro-1lambda~6~-thieno[3,2-e][1,2]thiazine-1,1(2H)-dioneYield 75%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of (S)-3,4-dihydro-6-chloro-4-hydroxy-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide (5, 1.2 g) and potassium carbonate (2.1 g) in dimethylsulfoxide (7 mL) was treated with 1-bromo-2-methoxyethane (0.5 eq, 0.25 mL) and the mixture was stirred at ambient temperature for 3 hours. Another 0.25 mL of 1-bromo-2-methoxyethane was then added and the mixture was stirred at ambient temperature for 18 hours. TLC analysis after this period indicated incomplete reaction, so another 0.25 mL of 1-bromo-2-methoxyethane was added and the mixture was stirred at ambient temperature for another 3 hours. At this point, TLC indicated complete reaction. The mixture was poured into saturated aqueous sodium chloride (50 mL) and extracted with t-butyl methyl ether. The organic phase was washed sequentially with 10% aqueous sodium hydroxide, 1:1 5.25% sodium hypochlorite water, and saturated aqueous sodium chloride, dried over sodium sulfate, and stripped of solvent by rotary evaporation. Residual solvent was removed under vacuum to provide 1.1 grams (75%) of (S)-3,4-dihydro-6-chloro-4-hydroxy-2-(2-methoxyethyl)-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide as a light yellow oil: IR (film) 3500-3400, 1430, 1340, 1170, 1120, 1080, 1040, 700 cm-1 ; 1H NMR (CDCl3) δ6.98 (s, 1H), 4.57 (br, 1H), 4.33 (dd, 1H, J=4 and 16 Hz), 4.16 (br, 1H), 3.91-3.38 (m, 5 H), 3.31 (s 3H); [α]25D +4.0° (c=1, CH3OH); Analysis for C9H12ClNO4S2 : Calcd: C, 36.30; H, 4.06; N, 4.70. Found: C, 36.23; H, 4.05; N, 4.66.

Workup

  1. stirringthe mixture was stirred at ambient temperature for 18 hours
  2. waitTLC analysis after this period indicated incomplete
  3. customreaction
  4. stirringthe mixture was stirred at ambient temperature for another 3 hours
  5. customreaction
  6. extractionextracted with t-butyl methyl ether
  7. washThe organic phase was washed sequentially with 10% aqueous sodium hydroxide, 1:1 5.25% sodium hypochlorite water, and saturated aqueous sodium chloride
  8. dry with materialdried over sodium sulfate
  9. customstripped of solvent by rotary evaporation
  10. customResidual solvent was removed under vacuum

Sources & evidence

ORD record
ord-763fb1fa301441c5a0a73e3bb8398ad1
Source dataset
uspto-grants-1994_09
Patent number
US05344929

Reaction notes

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