Hydrochloric Acid → HCID 67129726, compound

HRID 1184412Notes

Reaction equation

HRID 1184412 reaction equation
C([C@@H]1COC(=O)N1[C:14]([C@@H:16]1[CH2:28][CH2:27][C:19]2(OCC(C)(C)C[O:20]2)[CH2:18][C@H:17]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[F:35])=[O:15])C1C=CC=CC=1.[OH:36]O.[Li+].[OH-].Cl.C1(NC2CCCCC2)CCCCC1>C1COCC1>[F:35][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[C@@H:17]1[CH2:18][C:19](=[O:20])[CH2:27][CH2:28][C@H:16]1[C:14]([OH:15])=[O:36]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 7582DicyclohexylamineHCID 86692735HCID 86692735, compound

Product 1

HCID 67129726HCID 67129726, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The product from step 1 was dissolved in THF (200 mL) and cooled to 0° C. in an ice bath. Hydrogen peroxide (22.6 mL, 35%, 258 mmol), followed by LiOH (4.12 g, 172 mmol in 40 mL water) were added, and the mixture was allowed to warm to rt and stirred overnight to afford the acid intermediate [HPLC/MS: 323.2 (M+1); Rt=2.97 min]. To this solution was added aqueous HCl (21.5 mL, 12M) and the reaction was aged at 60° C. overnight. The reaction was cooled to rt and the organic phase was separated. The aqueous phase was extracted with EtOAc (200 mL). The organic portions were combined and dried with MgSO4, filtered and concentrated. The resulting crude product was dissolved in EtOAc (300 mL) and N-cyclohexylcyclohexanamine (18.9 mL, 95 mmol) was added over 2 min. The resulting slurry was aged for 1 h and filtered. The wet cake was washed with EtOAc (50 mL×4) and air dried on a fritted funnel. The salt was then suspended in aq NaHSO4 (200 mL, 2N) at rt and aged overnight. The reaction was extracted with EtOAc (200 mL), washed with water and brine, dried (MgSO4), filtered and concentrated to afford the title compound. HPLC/MS: 237.1 (M+1); Rt=2.13 min.

Workup

  1. additionwere added
  2. temperatureto warm to rt
  3. customto afford the acid intermediate [HPLC/MS: 323.2 (M+1); Rt=2.97 min]
  4. waitthe reaction was aged at 60° C. overnight
  5. temperatureThe reaction was cooled to rt
  6. customthe organic phase was separated
  7. extractionThe aqueous phase was extracted with EtOAc (200 mL)
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe resulting crude product was dissolved in EtOAc (300 mL)
  12. waitThe resulting slurry was aged for 1 h
  13. filtrationfiltered
  14. washThe wet cake was washed with EtOAc (50 mL×4) and air
  15. customdried on a fritted funnel
  16. waitThe salt was then suspended in aq NaHSO4 (200 mL, 2N) at rt and aged overnight
  17. extractionThe reaction was extracted with EtOAc (200 mL)
  18. washwashed with water and brine
  19. dry with materialdried (MgSO4)
  20. filtrationfiltered
  21. concentrationconcentrated

Sources & evidence

ORD record
ord-a1d6dea75d7b4d0ca6de1b52efdc9a73
Source dataset
uspto-grants-2014_03
Patent number
US08669252B2

Reaction notes

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