Hydrochloric Acid → HCID 67814706, compound

HRID 2401387Notes

Reaction equation

HRID 2401387 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:12]2[C:13]([CH3:26])=[N:14][O:15][C:16]=2[C@@H:17]([NH:19][S@](C(C)(C)C)=O)[CH3:18])=[C:6]([CH:11]=1)[C:7](OC)=[O:8].Cl.C([Mg]Cl)(C)C>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:12]3[C:13]([CH3:26])=[N:14][O:15][C:16]=3[C@H:17]([CH3:18])[NH:19][C:7](=[O:8])[C:6]=2[CH:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 67971396HCID 67971396, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 67814706HCID 67814706, compoundYield 85.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a round bottomed flask was added methyl 5-chloro-2-(5-((S)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)-3-methylisoxazol-4-yl)benzoate (3.37 g, 8.45 mmol), MeOH (48 mL), and HCl [2M in ether] (8.45 mL, 16.90 mmol). The reaction was stirred at room temperature for 30 min before concentrating. The crude residue was concentrated from toluene (2×) and hexane (1×) before being placed on a high vacuum line overnight. The crude residue (as an off-white foam) was dissolved in THF (100 mL) before cooling to −78° C. and addition of isopropylmagnesium chloride (15 mL, 30.0 mmol). The solution was stirred at −78° C. for 5 min before removal of the cold bath and warming the reaction to room temperature. The solution was quenched with saturated aqueous NH4Cl and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to afford a white solid. This material was purified via chiral SFC to afford the titled compound (1.9 g, 7.23 mmol); LC/MS m/z 263 [M+H]+.

Workup

  1. concentrationbefore concentrating
  2. concentrationThe crude residue was concentrated from toluene (2×) and hexane (1×)
  3. custombefore being placed on a high vacuum line overnight
  4. dissolutionThe crude residue (as an off-white foam) was dissolved in THF (100 mL)
  5. temperaturebefore cooling to −78° C.
  6. stirringThe solution was stirred at −78° C. for 5 min before removal of the cold bath
  7. temperaturewarming
  8. customthe reaction to room temperature
  9. customThe solution was quenched with saturated aqueous NH4Cl
  10. additiondiluted with EtOAc
  11. customThe layers were separated
  12. extractionthe aqueous layer was extracted with EtOAc
  13. washThe combined organic layers were washed with brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customto afford a white solid
  18. customThis material was purified via chiral SFC

Sources & evidence

ORD record
ord-910c8dce974949998b07548ca079f7a4
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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