Hydrochloric Acid → Vestipitant

HRID 1864091Notes

Reaction equation

HRID 1864091 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:33])[C:16]([N:18]2[CH2:23][CH2:22][NH:21][C:20](=O)[C@@H:19]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.B.C1COCC1.Cl.C([O-])(O)=O.[Na+]>C1COCC1.O>[F:35][C:2]([F:1])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:33])[C:16]([N:18]2[CH2:23][CH2:22][NH:21][CH2:20][C@@H:19]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 2723981Borane;tetrahydrofuranHCID 44138689HCID 44138689, compound

Product 1

HCID 9832383VestipitantYield 57.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of intermediate 40a (15.6 g) in anhydrous THF (94 ml), at 0° C., under N2, BH3THF 1M/THF (154 ml) was added. The solution was heated at reflux for 3 hr. HCl 37% (54 ml) was slowly added maintaining the reaction mixture in an ice-bath and the reaction mixture was stirred at rt for 1 hr. Water was then added (125 ml) and solid NaHCO3 (62.4 g) was added portionwise until a pH of 6.5. The aqueous phase was extracted with Et2O (4×160 ml) and the combined organic extracts were dried over Na2SO4, the solids were filtered and evaporated to leave a colourless oil which was purified by flash chromatography (silica gel, EtOAc/Methanol 7/3). The obtained product was suspended in Et2O (220 ml) and washed with NaHCO3 sat. (2×36 ml). The combined organic phases were dried (Na2SO4) and evaporated to give the title compound as white foam (8.7 g,).

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 3 hr
  3. temperaturemaintaining the reaction mixture in an ice-bath
  4. additionwas added portionwise until a pH of 6.5
  5. extractionThe aqueous phase was extracted with Et2O (4×160 ml)
  6. dry with materialthe combined organic extracts were dried over Na2SO4
  7. filtrationthe solids were filtered
  8. customevaporated
  9. customto leave a colourless oil which
  10. customwas purified by flash chromatography (silica gel, EtOAc/Methanol 7/3)
  11. washwashed with NaHCO3 sat. (2×36 ml)
  12. dry with materialThe combined organic phases were dried (Na2SO4)
  13. customevaporated

Sources & evidence

ORD record
ord-9e71b7516fea498ba684fe8630bb25b8
Source dataset
uspto-grants-2009_12
Patent number
US07625904B2

Reaction notes

Loading…