Potassium Hydroxide → cyclopentyl 2-cyclohexyl-2-((6-(3-(hydroxyamino)-3-oxopropyl)pyridin-3-yl)methylamino)acetate

HRID 919106Notes

Reaction equation

HRID 919106 reaction equation
[CH:1]1([C@H:7]([NH:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][CH2:25][C:26](OCC)=[O:27])=[N:22][CH:23]=2)[C:8]([O:10][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:32][OH:33].[OH-].[K+]>C(O)C.O>[CH:1]1([C@H:7]([NH:16][CH2:17][C:18]2[CH:23]=[N:22][C:21]([CH2:24][CH2:25][C:26]([NH:32][OH:33])=[O:27])=[CH:20][CH:19]=2)[C:8]([O:10][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 86691257HCID 86691257, compound

Product 1

HCID 53630042cyclopentyl 2-cyclohexyl-2-((6-(3-(hydroxyamino)-3-oxopropyl)pyridin-3-yl)methylamino)acetateYield 16.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Ethyl 3-[5-({[(1S)-1-cyclohexyl-2-(cyclopentyloxy)-2-oxoethyl]amino}methyl)pyridin-2-yl]propanoate (0.9 g, 2.16 mmol) and hydroxylamine hydrochloride (0.6 g, 8.64 mmol) were dissolved in ethanol (10 mL) then cooled to <5° C. Potassium hydroxide (0.97 g, 17.28 mmol) was dissolved in water (2.07 mL) and then charged to the reaction which was stirred at <5° C. for 20 min. The reaction was quenched to pH ˜7 and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was dissolved in hot EtOH (2 mL) and water (3 mL) added. On cooling some of the resulting solid (235 mg) was collected by filtration and dried to give cyclopentyl (2S)-cyclohexyl[({6-[3-(hydroxyamino)-3-oxopropyl]pyridin-3-yl}methyl)amino]ethanoate (147 mg).

Workup

  1. temperaturethen cooled to <5° C
  2. additioncharged to the reaction which
  3. customThe reaction was quenched to pH ˜7
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in hot EtOH (2 mL)
  9. additionwater (3 mL) added
  10. temperatureOn cooling some of the resulting solid (235 mg)
  11. filtrationwas collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-85ff07bfcb274c0da3a558b851387493
Source dataset
uspto-grants-2016_03
Patent number
US09273003B2

Reaction notes

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