1,2-Diaminocyclohexane, trans- → 1-[4-(4-Chlorophenoxy)phenyl]-5-phenylpyrrolidin-2-one

HRID 1972234Notes

Reaction equation

HRID 1972234 reaction equation
[C:1]1([CH:7]2[NH:11][C:10](=[O:12])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:14]1[CH:27]=[CH:26][C:17]([O:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[CH:16][CH:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C@@H]1(N)CCCC[C@H]1N>[Cu](I)I.O1CCOCC1>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([O:18][C:17]2[CH:26]=[CH:27][C:14]([N:11]3[CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:8][CH2:9][C:10]3=[O:12])=[CH:15][CH:16]=2)=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 956722-Pyrrolidinone, 5-phenyl-HCID 193519901-Chloro-4-(4-iodophenoxy)benzene

Product 1

HCID 569565971-[4-(4-Chlorophenoxy)phenyl]-5-phenylpyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Step A (Method 1, Using Standard Buchwald Coupling Conditions): To a 10 mL reaction tube fitted with a screw cap is charged with 5-phenylpyrrolidin-2-one (26.8 mg, 0.166 mmol), 1-(4-iodophenoxy)-4-chlorobenzene (66 mg, 0.199 mmol, 1.2 eq), copper iodide (6.3 mg, 0.033 mmol, 0.2 eq), K3PO4 (70.6 mg, 0.333 mmol, 2.0 eq), trans-cyclohexane-1,2-diamine (3.8 mg, 0.033 mmol, 0.2 eq) and 1,4-dioxane (2 mL). The system is degassed with argon then sealed and heated to 110° C. for 20 h. The reaction is cooled to room temperature, dissolved in ethyl acetate and washed with water and brine. The organic phase is dried over Na2SO4, filtered and concentrated in vacuo. Purification on silica gel (0-33% ethyl acetate in hexane) gives 1-[4-(4-chlorophenoxy)phenyl]-5-phenylpyrrolidin-2-one as a slightly brown oil (30.0 mg, 50%).

Workup

  1. customStep A (Method 1, Using Standard Buchwald Coupling Conditions): To a 10 mL reaction tube
  2. customfitted with a screw
  3. customcap
  4. customThe system is degassed with argon
  5. customthen sealed
  6. temperatureThe reaction is cooled to room temperature
  7. dissolutiondissolved in ethyl acetate
  8. washwashed with water and brine
  9. dry with materialThe organic phase is dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification on silica gel (0-33% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-08c805f1a3b7438aa2e5230e8a300014
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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