Ammonium Hydroxide → HCID 58481747, compound

HRID 1876925Notes

Reaction equation

HRID 1876925 reaction equation
[Cl-].[Ce+3].[Cl-].[Cl-].[CH:5]([Mg]Br)=[CH2:6].[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]=[CH:18][N:19]3[C:28]=2[CH:27]=[C:26]2[C:21]([CH3:30])([C:22](=[O:29])[CH2:23][CH2:24][CH2:25]2)[CH2:20]3)=[CH:12][CH:11]=1.[OH-].[NH4+].C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C>[F:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[N:17]=[CH:18][N:19]3[C:28]=2[CH:27]=[C:26]2[C:5]([CH3:6])([C:22]([CH:21]=[CH2:30])([OH:29])[CH2:23][CH2:24][CH2:25]2)[CH2:20]3)=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 14923Ammonium HydroxideHCID 24636Cerium(III) chlorideHCID 516892Sodium BicarbonateHCID 58481770HCID 58481770, compoundHCID 178418507HCID 178418507, compound

Product 1

HCID 58481747HCID 58481747, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To anhydrous cerium(III) chloride (274 mg, 1.1 mmol) was added anhydrous THF (4 mL) under nitrogen. The mixture was stirred at RT for 30 min before vinylmagnesium bromide (1.1 mL, 1.1 mmol) was added dropwise at −78° C. under a nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 30 min before a solution of 1-(4-fluorophenyl)-5a-methyl-5,5a,8,9-tetrahydroimidazo[1,5-b]isoquinolin-6(7H)-one (step a, 66 mg, 0.22 mmol) in anhydrous THF (2 mL) was added dropwise at the same temperature. The reaction mixture was stirred at −78° C. for 30 min and at RT for 1 hr. Concentrated aqueous ammonium hydroxide (1.5 mL) was added. The solid was filtered off through a celite pad and washed with ethyl acetate (3×2 mL). The organic filtrate was dried (Na2SO4), concentrated under reduced pressure, and dissolved in methanol (2 mL). Purification using reverse phase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA) gave 1-(4-fluorophenyl)-5a-methyl-6-vinyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-ol (40 mg, 0.12 mmol, 55% yield) as a glassy solid (after neutralization using saturated aqueous sodium bicarbonate solution and extraction with ethyl acetate). MS found: (M+H)+=325.2.

Workup

  1. additionwas added dropwise at −78° C. under a nitrogen atmosphere
  2. additionwas added dropwise at the same temperature
  3. filtrationThe solid was filtered off through a celite pad
  4. washwashed with ethyl acetate (3×2 mL)
  5. dry with materialThe organic filtrate was dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. dissolutiondissolved in methanol (2 mL)
  8. customPurification
  9. customphase HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)
  10. customgave

Sources & evidence

ORD record
ord-cd5f289fc7624527981cd775392a52df
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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