Tetrahydrofuran → cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane

HRID 2288762Notes

Reaction equation

HRID 2288762 reaction equation
C([N:8]1[CH2:15][C@@H:14]2[C@@H:10]([CH2:11][N:12]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=3[F:25])[CH2:13]2)[CH2:9]1)C1C=CC=CC=1.C1COCC1.C([O-])=O.[NH4+]>[Pd].CO>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([N:12]2[CH2:11][C@@H:10]3[C@@H:14]([CH2:15][NH:8][CH2:9]3)[CH2:13]2)=[C:17]([F:25])[CH:18]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 21969626cis-3-Benzyl-7-(2-fluoro-4-nitrophenyl)-3,7-diazabicyclo[3,3,0]octane

Product 1

HCID 70202150cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

cis-3-Benzyl-7-(2-fluoro-4-nitrophenyl)-3,7-diazabicyclo[3.3.0]octane (9.11 g, 26.71 mmol), THF (100 mL), and methanol (50 mL) are combined with 10% palladium on carbon (6.67 g) and ammonium formate (16.83 g, 266.90 mmol) under nitrogen, heated to reflux for 2.5 hours, cooled to ambient temperature, stirred 15 hours, filtered through celite and concentrated in vacuo to give crude cis-3-(4-amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane. cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane, water (100 mL), acetone (100 mL), and potassium carbonate (7.75 g, 56.07 mmol) are combined, cooled to 0° C., and benzyl chloroformate is added slowly. The reaction is warmed to ambient temperature, stirred 15 hours, concentrated in vacuo, and diluted with ethyl acetate. The organic phase is washed with water (2×150 mL) and saline (150 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with hexane/ethyl acetate (80/20). The appropriate fractions are combined (Rf =0.41, TLC, hexane/ethyl acetate, 50/50) and concentrated in vacuo to give the title compound, mp 121-122° C.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2.5 hours
  3. filtrationfiltered through celite and
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc8398273f7c47ee850ce4b94eaef61a
Source dataset
uspto-grants-2000_07
Patent number
US06090820

Reaction notes

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