Sodium Sulfite → 3-[5-(Tetrahydro-pyran-4-yl)-1,3-dihydro-isoindole-2-carbonyl]-4-((s)-2,2,2-trifluoro-1-methyl-ethoxy)-benzenesulfinate sodium salt

HRID 1690778Notes

Reaction equation

HRID 1690778 reaction equation
[O-]S([O-])=O.[Na+:5].[Na+].[O:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[CH2:18][N:17]([C:22]([C:24]2[CH:25]=[C:26]([S:37](Cl)(=[O:39])=[O:38])[CH:27]=[CH:28][C:29]=2[O:30][C@@H:31]([CH3:36])[C:32]([F:35])([F:34])[F:33])=[O:23])[CH2:16]3)[CH2:9][CH2:8]1.C([O-])(O)=O.[Na+]>O>[Na+:5].[O:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[CH2:18][N:17]([C:22]([C:24]2[CH:25]=[C:26]([S:37]([O-:39])=[O:38])[CH:27]=[CH:28][C:29]=2[O:30][C@@H:31]([CH3:36])[C:32]([F:34])([F:35])[F:33])=[O:23])[CH2:16]3)[CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 24437Sodium SulfiteHCID 516892Sodium BicarbonateHCID 56851160HCID 56851160, compound

Product 1

HCID 568511613-[5-(Tetrahydro-pyran-4-yl)-1,3-dihydro-isoindole-2-carbonyl]-4-((s)-2,2,2-trifluoro-1-methyl-ethoxy)-benzenesulfinate sodium saltYield 48%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
37.5 °C

Procedure

1.15 g (8.94 mmol) of Na2SO3 and 1.70 g (9.60 mmol) of Na2HPO4 hydrate were dissolved in 13 ml water. An ethanolic solution of 2.40 g (4.63 mmol) of 3-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindole-2-carbonyl]-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzenesulfonyl chloride was added. The reaction mixture was stirred at 35 to 40° C. during 1 hour and then overnight at room temperature. 1.3 g Speedex was added, the reaction mixture was filtered and the filtrate was evaporated. The crude product was treated with aqueous citric acid/NaCl solution then extracted with MTBE/THF 1:1. The organic solvent was evaporated and the residue was dissolved in MeOH/water (2:1), and treated with 800 mg (9.52 mmol) of NaHCO3. 1 g Speedex was added and the reaction mixture was filtrated and concentrated in vacuo. The residue was purified chromatographically by using a reverse phase column (RP-18, water/methanol) to provide 1.12 g (48%) of the title compound as a white foam. MS (m/e): 484.3 [M+H]+.

Workup

  1. customovernight
  2. customat room temperature
  3. addition1.3 g Speedex was added
  4. filtrationthe reaction mixture was filtered
  5. customthe filtrate was evaporated
  6. additionThe crude product was treated with aqueous citric acid/NaCl solution
  7. extractionthen extracted with MTBE/THF 1:1
  8. customThe organic solvent was evaporated
  9. dissolutionthe residue was dissolved in MeOH/water (2:1)
  10. addition1 g Speedex was added
  11. filtrationthe reaction mixture was filtrated
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified chromatographically

Sources & evidence

ORD record
ord-770876c0155c4979912b5baf0b37c5dc
Source dataset
uspto-grants-2012_04
Patent number
US08153679B2

Reaction notes

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