1,2-Diaminocyclohexane → (S)-3-(2-methyl-1H-benzo[d]imidazol-6-yl)-4-phenyloxazolidin-2-one

HRID 706304Notes

Reaction equation

HRID 706304 reaction equation
F[C:2](F)(F)[C:3]([O-])=O.[C:8]1([C@H:14]2[CH2:18][O:17][C:16](=[O:19])[NH:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.I[C:21]1[CH:22]=[C:23]([NH2:28])[C:24]([NH2:27])=[CH:25][CH:26]=1.[F-].[Cs+].C1(N)CCCCC1N>[Cu]I>[CH3:2][C:3]1[NH:28][C:23]2[CH:22]=[C:21]([N:15]3[C@@H:14]([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)[CH2:18][O:17][C:16]3=[O:19])[CH:26]=[CH:25][C:24]=2[N:27]=1

Participants

7

Reactant 5

HCID 46101,2-DiaminocyclohexaneHCID 25953Cesium fluorideHCID 84468TrifluoroacetateHCID 7304242-Oxazolidinone, 4-phenyl-, (4S)-HCID 112070494-Iodobenzene-1,2-diamine

Product 1

HCID 51030216(S)-3-(2-methyl-1H-benzo[d]imidazol-6-yl)-4-phenyloxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
95 °C

Procedure

The compound was synthesized as trifluoroacetate salt starting from (S)-4-phenyloxazolidin-2-one (1 equiv., 0.163 g, 1 mmol), 4-iodobenzene-1,2-diamine (1 equiv., 0.234 g, 1 mmol), copper(I) iodide (0.1 equiv., 0.019 g, 0.1 mmol), cesium fluoride (2 equiv., 0.304 g, 2 mmol), cyclohexane-1,2-diamine (0.1 equiv., 0.012 mL, 0.1 mmol). The solids were given together in a reaction flask and the flask was purged with argon. A solution of cyclohexane-1,2-diamine in 4 mL dioxane was added to the flask. The reaction was stirred at 95° C. for 20 hours, before the reaction was cooled down to 45° C. and filtered through a pad of celite. The pad was washed with warm dichloromethane and the solution was concentrated under reduced pressure. The intermediate product was purified via FPLC using a chloroform-methanol gradient (0→10%, product elutes at about 5%). Yield: 0.215 g (80%); MS m/z 270.3 (M+H)+ The (S)-3-(3,4-diaminophenyl)-4-phenyloxazolidin-2-one was dissolved in 12 mL of triethyl orthoacetate and the reaction was stirred at 150° C. for 0.5 h before the reaction was cooled down. The excess of triethyl orthoacetate was removed under reduced pressure. The final product was purified by means of FPLC using chloroform-methanol gradient (0→10%), followed by preparative HPLC using a water-acetonitrile gradient with 0.04% trifluoroacetic acid.

Workup

  1. customThe solids were given together in a reaction flask
  2. customthe flask was purged with argon
  3. additionA solution of cyclohexane-1,2-diamine in 4 mL dioxane was added to the flask
  4. temperaturewas cooled down to 45° C.
  5. filtrationfiltered through a pad of celite
  6. washThe pad was washed with warm dichloromethane
  7. concentrationthe solution was concentrated under reduced pressure
  8. customThe intermediate product was purified via FPLC
  9. dissolutionMS m/z 270.3 (M+H)+ The (S)-3-(3,4-diaminophenyl)-4-phenyloxazolidin-2-one was dissolved in 12 mL of triethyl orthoacetate
  10. stirringthe reaction was stirred at 150° C. for 0.5 h before the reaction
  11. temperaturewas cooled down
  12. customThe excess of triethyl orthoacetate was removed under reduced pressure
  13. customThe final product was purified by means of FPLC

Sources & evidence

ORD record
ord-a13a4dcc91764f6c91d7f9222fe4cb80
Source dataset
uspto-grants-2015_11
Patent number
US09173885B2

Reaction notes

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