Methanesulfonic Acid → 1352398-60-7

HRID 1431210Notes

Reaction equation

HRID 1431210 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[C:7](=[O:12])[CH2:6][CH2:5]2.CS(O)(=O)=O.[N-:18]=[N+]=[N-].[Na+].[OH-].[Na+]>[Cl-].[Na+].O.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[C:7](=[O:12])[NH:18][CH2:6][CH2:5]2

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 117895955,7-DIFLUORO-1-INDANONE

Product 1

HCID 667426241352398-60-7Yield 76.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer, was charged with 5,7-difluoro-2,3-dihydro-1H-indene-1-one (10 g, 59.4 mmol) followed by dry dichloromethane (100 ml) and methanesulfonic acid (71.3 ml, 1.1 mol). The reaction was cooled to 0° C. (ice bath) and to this was added sodium azide (5.41 g; 83.2 mmol) in 4 equal portions over 20 minutes. The reaction was stirred at 0° C. for 2 hours and then a 20% aqueous solution of sodium hydroxide (175 ml) was added over 30 minutes with vigorous stirring. After complete addition the mixture was transferred to a separatory funnel and the methylene chloride phase was isolated. This was shaken with an equal volume of 50% diluted brine solution. The organic phase was collected and the aqueous phases were back extracted with dichloromethane (2×80 ml). The organic phases were combined, dried (magnesium sulfate), filtered and concentrated in vacuo. The crude residue was purified via HPLC on silica gel, eluting with 40% to 95% ethyl acetate/hexanes to provide the desired product as a white solid (8.364 g). (M+H)+=184 m/e.

Workup

  1. customA 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer
  2. additionAfter complete addition the mixture
  3. customwas transferred to a separatory funnel
  4. customThe organic phase was collected
  5. extractionthe aqueous phases were back extracted with dichloromethane (2×80 ml)
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified via HPLC on silica gel
  10. washeluting with 40% to 95% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5a547b18764347daaf3467c6751ff832
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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