Sulfuryl chloride → (5R)-3-(4-(1-Isopropylsulfonyl-1,2,5,6-tetrahydropyridin-4-yl)-3-fluoro-phenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one

HRID 723799Notes

Reaction equation

HRID 723799 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[CH:23][N:22]=[N:21]4)[O:16][C:15]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1.C(=O)(O)[O-].[Na+].[CH:32]([S:35](Cl)(=[O:37])=[O:36])([CH3:34])[CH3:33].S(Cl)(Cl)(=O)=O>O.CC(C)=O>[CH:32]([S:35]([N:2]1[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]4[CH:24]=[CH:23][N:22]=[N:21]4)[O:16][C:15]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1)(=[O:37])=[O:36])([CH3:34])[CH3:33]

Participants

7

Reactant 4

HCID 24648Sulfuryl chlorideHCID 824082-Propanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 69364214(5R)-3-(4-(1,2,5,6-Tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)-oxazolidin-2-one hydrochloride

Product 1

HCID 69366716(5R)-3-(4-(1-Isopropylsulfonyl-1,2,5,6-tetrahydropyridin-4-yl)-3-fluoro-phenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-oneYield 45.6%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

(5R)-3-(4-(1,2,5,6-Tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)-oxazolidin-2-one hydrochloride (380 mg, 1 mM) was dissolved in water (5 ml), which was then diluted with acetone (10 ml), and solid sodium bicarbonate (0.84 g, 10 mM) added. The mixture was stirred and cooled to 0° C., and isopropylsulfonyl chloride (285 mg, 2 mM) added dropwise. After stirring for 5 hours, an equal portion of sulfonyl chloride was added, and stirring continued for 18 hours. Most acetone was removed by evaporation, the residue diluted with water (50 ml), and extracted with ethyl acetate (3×20 ml). The extracts were washed with brine and dried (magnesium sulfate). The residual oil after evaporation was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (205 mg).

Workup

  1. additionadded
  2. stirringAfter stirring for 5 hours
  3. stirringstirring
  4. customMost acetone was removed by evaporation
  5. additionthe residue diluted with water (50 ml)
  6. extractionextracted with ethyl acetate (3×20 ml)
  7. washThe extracts were washed with brine
  8. dry with materialdried (magnesium sulfate)
  9. customThe residual oil after evaporation
  10. customwas purified by chromatography on a 10 g silica Mega Bond Elut® column
  11. washeluting with
  12. temperaturea gradient increasing in polarity from 0 to 5% methanol in dichloromethane
  13. customevaporated

Sources & evidence

ORD record
ord-47e740d465ec44c3b8a2abaa00d76422
Source dataset
uspto-grants-2006_11
Patent number
US07141583B2

Reaction notes

Loading…