Ammonia → N~1~-{2-Cyano-2-[3-(cyclopentyloxy)-4-methoxyphenyl]ethyl}ethanediamide

HRID 275493Notes

Reaction equation

HRID 275493 reaction equation
[C:1]([C:3]1([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:16]=2)C=CC=C[CH:4]1[NH:9][C:10](=[O:14])[C:11]([O-])=[O:12])#[N:2].O.[OH-].[Li+].C[N:33]1CCOCC1.C(OC(Cl)=O)C(C)C.N>CO>[C:1]([CH:3]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:16]=1)[CH2:4][NH:9][C:10]([C:11]([NH2:33])=[O:12])=[O:14])#[N:2]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 168937Lithium hydroxide, monohydrateHCID 20088261HCID 20088261, compound

Product 1

HCID 20088272N~1~-{2-Cyano-2-[3-(cyclopentyloxy)-4-methoxyphenyl]ethyl}ethanediamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

N-[2-cyano-2-(3-cyclopentyloxy-4-methoxyphenyl)phenyl]oxamate (332 mg, 0.96 mmol) in methanol (3 mL) was treated with lithium hydroxide monohydrate (126 mg, 2.88 mmol) and stirred for 5 min. The solvent was removed in vacuo, the resin acidified with 10% aqueous hydrochloric acid and partitioned between methylene chloride and water and extracted. The organic extract was dried (magnesium sulfate) and evaporated. The residue was dissolved in ethylene gylcol dimethyl ether (5 mL) and treated with N-methylmorpholine (127 mL, 1.15 mmol) and isobutylchloroformate (143 mL, 1.1 mmol). After 10 min, the reaction was cooled to 0° C. and a solution of ammonia-saturated ethylene glycol dimethyl ether (5-10 mL) was added. The reaction was allowed to stir for 0.5 h at 0° C. and for 2 h at room temperature. The mixture was partitioned between methylene chloride/methanol and water and washed with 10% aqueous hydrochloric acid and water. The organic extract was dried (magnesium sulfate) and evaporated to a white solid. Purification by flash chromatography, eluting with 1:1 ethyl acetate/hexanes, provided a white solid which was triturated with ether, filtered and dried (106.2 mg, 33%): m.p. 176°-177° C.

Workup

  1. customThe solvent was removed in vacuo
  2. custompartitioned between methylene chloride and water
  3. extractionextracted
  4. extractionThe organic extract
  5. dry with materialwas dried (magnesium sulfate)
  6. customevaporated
  7. dissolutionThe residue was dissolved in ethylene gylcol dimethyl ether (5 mL)
  8. waitAfter 10 min
  9. stirringto stir for 0.5 h at 0° C. and for 2 h at room temperature
  10. customThe mixture was partitioned between methylene chloride/methanol and water
  11. washwashed with 10% aqueous hydrochloric acid and water
  12. extractionThe organic extract
  13. dry with materialwas dried (magnesium sulfate)
  14. customevaporated to a white solid
  15. customPurification by flash chromatography
  16. washeluting with 1:1 ethyl acetate/hexanes
  17. customprovided a white solid which
  18. customwas triturated with ether
  19. filtrationfiltered
  20. customdried (106.2 mg, 33%)

Sources & evidence

ORD record
ord-352cb269f4394c5bac34735173b94336
Source dataset
uspto-grants-1995_02
Patent number
US05393788

Reaction notes

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