Sulfuric acid magnesium salt (1:1) → HCID 66800094, compound

HRID 1528299Notes

Reaction equation

HRID 1528299 reaction equation
[CH3:1][C:2]1([CH3:12])[CH2:11][NH:10][C@H:9]2[C@H:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[NH:3]1.Br[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[H+].[B-](F)(F)(F)F.CC([O-])(C)C.[Na+].[O-]S([O-])(=O)=O.[Mg+2]>CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O.O.C1(C)C=CC=CC=1>[ClH:21].[Cl:21][C:16]1[CH:15]=[C:14]([N:10]2[C@H:9]3[C@H:4]([CH2:5][CH2:6][CH2:7][CH2:8]3)[NH:3][C:2]([CH3:12])([CH3:1])[CH2:11]2)[CH:19]=[CH:18][C:17]=1[F:20]

Participants

11

Reactant 6

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 28118Tetrafluoroboric acidHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 35430654-Bromo-2-chloro-1-fluorobenzeneHCID 22810137HCID 22810137, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 66800094HCID 66800094, compoundYield 76.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A toluene (10 ml) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (168 mg, 0.998 mmol), 4-bromo-2-ch1oro-1-fluorobenzene (251 mg, 1.20 mmol), Pd(OAc)2 (11.2 mg, 0.0500 mmol), t-Bu3P.HBF4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 5 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO4 was further added thereto, and the mixture was stirred. Then, insoluble matter was filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt). The obtained oil was dissolved in 1 N HCl-EtOH (3 mL), and ethanol was distilled off under reduced pressure. The deposited crystal was recrystallized from ethanol/acetone to obtain (4aS,8aR)-1-(3-chloro-4-fluorophenyl)-3,3-dimethyldecahydroquinoxaline hydrochloride (153 mg, yield: 46%) in a white powder form.

Workup

  1. temperatureunder reflux in a nitrogen atmosphere
  2. stirringthe mixture was stirred
  3. filtrationThen, insoluble matter was filtered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt)
  6. dissolutionThe obtained oil was dissolved in 1 N HCl-EtOH (3 mL)
  7. distillationethanol was distilled off under reduced pressure
  8. customThe deposited crystal was recrystallized from ethanol/acetone

Sources & evidence

ORD record
ord-fc55887659ca471e9b9ea4fa16ec334e
Source dataset
uspto-grants-2015_07
Patent number
US09090572B2

Reaction notes

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