Sulfuric acid magnesium salt (1:1) → HCID 56945051, compound

HRID 1528302Notes

Reaction equation

HRID 1528302 reaction equation
[NH:1]1[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[NH:4][CH2:3][C:2]21[CH2:13][CH2:12][CH2:11]2.Br[C:15]1[C:20]2[CH:21]=[CH:22][O:23][C:19]=2[C:18]([O:24][CH3:25])=[CH:17][CH:16]=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>[CH3:25][O:24][C:18]1[C:19]2[O:23][CH:22]=[CH:21][C:20]=2[C:15]([N:4]2[C@H:5]3[C@H:10]([CH2:9][CH2:8][CH2:7][CH2:6]3)[NH:1][C:2]3([CH2:13][CH2:12][CH2:11]3)[CH2:3]2)=[CH:16][CH:17]=1

Participants

11

Reactant 6

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 28118Tetrafluoroboric acidHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 23676156Sodium t-butoxideHCID 583162504-bromo-7-methoxybenzofuranHCID 66806677HCID 66806677, compound

Product 1

HCID 56945051HCID 56945051, compoundYield 35%

Reagents, catalysts & solvents 4

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

Procedure

A toluene (4 ml) suspension of (4a′R,8a′S)-octahydro-1′H -spiro[cyclobutane-1,2′-quinoxaline](180 mg, 0.998 mmol), 4-bromo-7-methoxybenzofuran (250 mg, 1.10 mmol), Pd(OAc)2 (11.2 mg, 0.0499 mmol), t-Bu3P.HBF4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 4 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. Insoluble matter was filtered, and the residue was washed with AcOEt (5 mL×2). Then, the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a colorless amorphous solid. This solid was crystallized from hexane (1 mL) to obtain (4a′R,8a′S)-4′-(7-methoxybenzofuran-4-yl)octahydro-1′H-spiro[cyclobutane-1,2′-quinoxaline](107 mg, yield: 35%) in a white powder form.

Workup

  1. temperatureunder reflux in a nitrogen atmosphere
  2. stirringthe mixture was stirred
  3. filtrationInsoluble matter was filtered
  4. washthe residue was washed with AcOEt (5 mL×2)
  5. concentrationThen, the filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt)
  7. customto obtain a colorless amorphous solid
  8. customThis solid was crystallized from hexane (1 mL)

Sources & evidence

ORD record
ord-bfb5f5c1bfa343a585848e560125870d
Source dataset
uspto-grants-2015_07
Patent number
US09090572B2

Reaction notes

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