Hydroxylamine → Furo[3,2-c]pyridin-4-amine

HRID 1875892Notes

Reaction equation

HRID 1875892 reaction equation
Cl[C:2]1[C:7]2[CH:8]=[CH:9][O:10][C:6]=2[CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].C(=[NH:30])(C1C=CC=CC=1)C1C=CC=CC=1.NO>C1(C)C=CC=CC=1.CCOCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[O:10]1[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:30])[C:7]=2[CH:8]=[CH:9]1

Participants

9

Reactant 4

HCID 787HydroxylamineHCID 136809Benzophenone imineHCID 27797464-Chlorofuro[3,2-c]pyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 22665882Furo[3,2-c]pyridin-4-amineYield 89.1%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

To 4-chlorofuro[3,2-c]pyridine (1 g, 6.5 mmol) in toluene under nitrogen was added racemic BINAP (0.243 g, 0.4 mmol), Pd2(dba)3 (0.12 g, 0.13 mmol) and sodium tert-butoxide (0.88 g, 9.1 mmol). Benzophenoneimine (1.3 mL, 7.81 mmol) was added and the mixture was heated to 80° C. for 3 h and cooled to room temperature. The reaction mixture was diluted with ether, filtered through Celite, and washed with ether. The filtrate was concentrated and the deep orange residue was taken up in methanol (90 ml) and treated with hydroxylamine (1.2 mL, 19.5 mmol). The mixture was stirred at ambient temperature for 18 h and concentrated. The residue was purified by column chromatography (95-100% ethyl acetate/hexanes) to afford furo[3,2-c]pyridin-4-amine (776 mg, 5.79 mmol, 89% yield) as a deep orange solid. MS (LC/MS) R.T.=0.51; [M+H]+=135.02.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through Celite
  3. washwashed with ether
  4. concentrationThe filtrate was concentrated
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (95-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-96fe30b4ff414229950cf184beb81925
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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