Citric Acid → HCID 50990949, compound

HRID 1777273Notes

Reaction equation

HRID 1777273 reaction equation
[OH:1][N:2]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH2:23]([O:27][C:28]1[CH:47]=[CH:46][C:31]([C:32]([NH:34][CH2:35][C@H:36]([N:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[C:37](O)=[O:38])=[O:33])=[CH:30][CH:29]=1)[C:24]#[C:25][CH3:26].[Si](ON)(C(C)(C)C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[CH2:23]([O:27][C:28]1[CH:47]=[CH:46][C:31]([C:32]([NH:34][CH2:35][C@@H:36]([C:37](=[O:38])[NH:2][OH:1])[N:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)=[O:33])=[CH:30][CH:29]=1)[C:24]#[C:25][CH3:26]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 67056339HCID 67056339, compound

Product 1

HCID 50990949HCID 50990949, compoundYield 13.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

270 mg (2.0 mmol) of 1-hydroxybenzotriazole and 390 mg (2.0 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride are added successively to a solution of 580 mg (1.7 mmol) of (S)-3-(4-but-2-ynyloxybenzoylamino)-2-piperidin-1-ylpropanoic acid in 15 ml of dimethylformamide. The reaction medium is stirred for 30 min at ambient temperature then 300 mg (2.0 mmol) of O-tert-butyldimethylsilylhydroxylamine in 5 ml of dimethylformamide are added. After stirring at ambient temperature for 18 h then hydrolysis with 2 ml of an aqueous solution of 5% citric acid, the reaction medium is stirred at ambient temperature for a further 30 min, then extracted with ethyl acetate. The ethyl acetate phase is washed with a saturated aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated. The residue obtained is purified by chromatography over silica gel eluted with a 98/2 dichloromethane/methanol mixture. 80 mg (13%) of 4-but-2-ynyloxy-N—((S)-2-hydroxycarbamoyl-2-piperidin-1-ylethyl)benzamide are obtained in the form of a white solid having a melting point of 144° C.

Workup

  1. stirringAfter stirring at ambient temperature for 18 h
  2. stirringthe reaction medium is stirred at ambient temperature for a further 30 min
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate phase is washed with a saturated aqueous solution of sodium hydrogen carbonate
  5. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue obtained
  9. customis purified by chromatography over silica gel
  10. washeluted with a 98/2 dichloromethane/methanol mixture

Sources & evidence

ORD record
ord-5bcf9ee10b2146aaa11d2a4773a206a3
Source dataset
uspto-grants-2016_02
Patent number
US09266848B2

Reaction notes

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