1-Hydroxybenzotriazole → HCID 49854306, compound

HRID 1620381Notes

Reaction equation

HRID 1620381 reaction equation
[OH:1][N:2]1C2C=CC=CC=2N=N1.[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([NH:28][CH2:29][C@H:30]([N:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[C:31]([OH:33])=O)(=[O:27])=[O:26])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Si](ON)(C(C)(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([NH:28][CH2:29][C@H:30]([N:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[C:31]([NH:2][OH:1])=[O:33])(=[O:27])=[O:26])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 66871907HCID 66871907, compound

Product 1

HCID 49854306HCID 49854306, compoundYield 34.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

150 mg (1.1 mmol) of 1-hydroxybenzotriazole and 210 mg (1.1 mmol) of 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide hydrochloride are added to a solution of 420 mg (1.0 mmol) of (S)-3-(4-benzyloxybenzenesulfonylamino)-2-piperidin-1-ylpropanoic acid in 15 ml of dimethylformamide. The reaction medium is stirred for 20 min and then a solution of 160 mg (1.1 mmol) of O-tert-butyldimethylsilylhydroxylamine in 3 ml of dimethylformamide is added. The reaction medium is then stirred at ambient temperature for 18 h and then hydrolyzed with 2 ml of a saturated aqueous solution of sodium hydrogen carbonate and 2 ml of water. After stirring for 20 min in order to complete the deprotection of the hydroxamate, the product is extracted with ethyl acetate. The organic phases are washed with a saturated aqueous solution of sodium hydrogen carbonate and then with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue obtained is crystallized from isopropyl ether under hot conditions, and then filtered off. The resulting solid is recrystallized from a 1/1 heptane/ethyl acetate mixture, filtered and then oven-dried under vacuum for 4 h. 150 mg of (S)-3-(4-benzyloxybenzenesulfonylamino)-N-hydroxy-2-piperidin-1-ylpropionamide are obtained in the form of a beige solid with a melting point of 126° C.

Workup

  1. stirringThe reaction medium is then stirred at ambient temperature for 18 h
  2. stirringAfter stirring for 20 min in order
  3. extractionthe product is extracted with ethyl acetate
  4. washThe organic phases are washed with a saturated aqueous solution of sodium hydrogen carbonate
  5. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue obtained
  9. customis crystallized from isopropyl ether under hot conditions
  10. filtrationfiltered off
  11. customThe resulting solid is recrystallized from a 1/1 heptane/ethyl acetate mixture
  12. filtrationfiltered
  13. customoven-dried under vacuum for 4 h

Sources & evidence

ORD record
ord-777c258f93e64bc2bd4f37f346ad1d78
Source dataset
uspto-grants-2014_07
Patent number
US08772478B2

Reaction notes

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