Potassium Carbonate → HCID 178426493, compound

HRID 1993874Notes

Reaction equation

HRID 1993874 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4][CH2:3]1.F[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:12]([O:11][C:9](=[O:10])[NH:8][C@H:5]1[CH2:6][CH2:7][C@@H:2]([NH:1][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=2[N+:24]([O-:26])=[O:25])[CH2:3][CH2:4]1)([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1362874-Fluoro-3-nitrotolueneHCID 178418966HCID 178418966, compound

Product 1

HCID 178426493HCID 178426493, compoundYield 90.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of tert-butyl cis-4-aminocyclohexanecarbamate (1.27 g, 5.93 mmol) and 4-fluoro-3-nitrotoluene (0.92 g, 5.93 mmol) in DMF (20 mL) was added potassium carbonate (1.64 g, 11.88 mmol). The mixture was heated at 85° C. and stirred overnight. The mixture was cooled to room temperature and the solid was filtered. The filtrate was evaporated to dryness. The residue was extracted with ethyl acetate and brine. The organic layer was dried over sodium sulfate and solvents were evaporated. The resulting material was purified through flash column chromatography using hexanes and ethyl acetate (4:1) to give an orange colored solid as cis-[4-(4-methyl-2-nitro-phenylamino)-cyclohexyl]-carbamic acid tert-butyl ester (1.88 g). This material (1.80 g, 5.17 mmol) was suspended in a mixture of methanol (50 mL) and water (25 mL). To this suspension was added ammonium chloride (4.15 g, 77.6 mmol) and zinc dust (3.36 g, 51.6 mmol). The mixture was stirred at room temperature for 20 minutes and THF (20 mL) was added. The mixture was stirred an additional 1 hr during which the orange color disappeared. The mixture was filtered and rinsed with THF and ethyl acetate. The filtrate was extracted with brine and ethyl acetate. Solvents were evaporated to give cis-[4-(2-amino-4-methyl-phenylamino)-cyclohexyl]-carbamic acid tert-butyl ester (1.65 g). LC-MS showed a single peak, C18H29N3O2 (m/e) calcd 319.2260, obsd 320.3 (M+H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationthe solid was filtered
  3. customThe filtrate was evaporated to dryness
  4. extractionThe residue was extracted with ethyl acetate and brine
  5. dry with materialThe organic layer was dried over sodium sulfate and solvents
  6. customwere evaporated
  7. customThe resulting material was purified through flash column chromatography

Sources & evidence

ORD record
ord-60ddd89fc01b49a79754ccef9a2892e0
Source dataset
uspto-grants-2010_01
Patent number
US07652053B2

Reaction notes

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