Potassium Carbonate → HCID 90413529, compound

HRID 1526532Notes

Reaction equation

HRID 1526532 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:9]2([CH2:17][F:18])[C@@H:15]3[C@@H:13]([CH2:14]3)[O:12][C:11]([NH2:16])=[N:10]2)[C:5]([F:8])=[N:6][CH:7]=1.FC(F)(F)C([NH2:23])=O.C(=O)([O-])[O-].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>C(Cl)Cl.[Cu]I.O1CCOCC1>[NH2:23][C:2]1[CH:3]=[C:4]([C@:9]2([CH2:17][F:18])[C@@H:15]3[C@@H:13]([CH2:14]3)[O:12][C:11]([NH2:16])=[N:10]2)[C:5]([F:8])=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 67717TrifluoroacetamideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 90412194HCID 90412194, compound

Product 1

HCID 90413529HCID 90413529, compoundYield 75.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A sealable vial was charged with (1R,5S,6R)-5-(5-bromo-2-fluoropyridin-3-yl)-5-(fluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (8f-B, 0.1016 g, 0.319 mmol), trifluoroacetamide (0.072 g, 0.639 mmol), copper(I) iodide (0.018 g, 0.096 mmol) and potassium carbonate (0.177 g, 1.278 mmol), followed by dioxane (1.8 mL) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.015 mL, 0.096 mmol). The reaction mixture was purged with nitrogen for 5 min and then heated at 120° C. for 20 h. The cooled reaction mixture was diluted with CH2Cl2 and washed with aqueous saturated NaHCO3 solution. The layers were separated and the aqueous layer was extracted with 15% MeOH/CH2Cl2. The combined organic extracts were dried over MgSO4 and the filtrate was concentrated in vacuo. The residue was purified by silica gel flash chromatography (1% to 10% MeOH/CH2Cl2) afforded the title compound (0.061 g, 0.240 mmol, 75% yield) as a tan amorphous solid. MS (ESI, positive ion) m/z: 255.1 (M+H)

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 min
  2. customThe cooled reaction mixture
  3. washwashed with aqueous saturated NaHCO3 solution
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with 15% MeOH/CH2Cl2
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe residue was purified by silica gel flash chromatography (1% to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d6d6c16fcd7b44e2912e390542aa3375
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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