N-Hydroxysuccinimide → 2,5-Dioxopyrrolidin-1-yl hept-6-ynoate

HRID 2425067Notes

Reaction equation

HRID 2425067 reaction equation
[C:1]([OH:9])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[CH:7].O[N:11]1[C:15](=[O:16])[CH2:14][CH2:13][C:12]1=[O:17].Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:12]1(=[O:17])[N:11]([O:8][C:1](=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[CH:7])[C:15](=[O:16])[CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 80170N-HydroxysuccinimideHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 43779506-Heptynoic acid

Product 1

HCID 866368782,5-Dioxopyrrolidin-1-yl hept-6-ynoateYield 73.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-heptynoic acid (5) (≧97%, TCI, Portland, Oreg.) (1 g, 7.9 mmol, 1 equiv.) was dissolved in 100 ml of anhydrous methylene chloride. N-hydroxysuccinimide (NHS) (98+%, Acros, New Jersey) (2.3 g, 19.8 mmol, 2.5 equiv.) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (98+%, Alfa Aesar) (2.3 g, 11.9 mmol, 1.5 equiv.) was added to the above solution. The resulting reaction mixture was stirred at room temperature overnight (18 hours) before 500 ml of a saturated sodium bicarbonate aqueous solution was added to it. The aqueous phase was extracted with 500 ml of ether. The ether extract was combined with the methylene chloride phase, washed with 500 ml of water and 500 ml of brine, and then dried with anhydrous magnesium sulfate. After magnesium sulfate was filtered away and the solvent was removed by rotary evaporation, an off-white solid (1.3 g, 72% yield) was obtained after being further dried overnight under vacuum. This solid was then used directly in the next step.

Workup

  1. customThe resulting reaction mixture
  2. additionwas added to it
  3. extractionThe aqueous phase was extracted with 500 ml of ether
  4. extractionThe ether extract
  5. washwashed with 500 ml of water and 500 ml of brine
  6. dry with materialdried with anhydrous magnesium sulfate
  7. filtrationAfter magnesium sulfate was filtered away
  8. customthe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-c9b0b705ebae4ab68152c536becf2d8f
Source dataset
uspto-grants-2011_06
Patent number
US07964636B2

Reaction notes

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