Ethanol → HCID 86758041, compound

HRID 1934403Notes

Reaction equation

HRID 1934403 reaction equation
[Li+].[OH-].C([O:5][C:6](=[O:37])[CH2:7][C@@H:8]([C:35]#[CH:36])[NH:9][C:10]([C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18](=[O:34])/[CH:19]=[CH:20]\[CH:21]2[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]2)[CH2:13]1)=[O:11])C.CCO.O>O1CCCC1>[NH:24]1[CH2:23][CH2:22][CH:21](/[CH:20]=[CH:19]\[C:18]([N:14]2[CH2:15][CH2:16][CH2:17][C@@H:12]([C:10]([NH:9][C@H:8]([C:35]#[CH:36])[CH2:7][C:6]([OH:37])=[O:5])=[O:11])[CH2:13]2)=[O:34])[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 86758042HCID 86758042, compound

Product 1

HCID 86758041HCID 86758041, compoundYield 67.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1N aqueous LiOH (3.0 ml) was added to a solution of N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(Z)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine ethyl ester (1.0 g) in tetrahydrofuran (5 ml)-EtOH (5 ml) at 0° C. The reaction mixture was stirred for 2 hours at room temperature, then water was added, and the whole was washed with diethyl ether. The aqueous layer was made acidic with 20% aqueous KHSO4, and extracted with ethyl acetate. The organic layer was dried over MgSO4, evaporated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and 4N HCl in ethyl acetate (5.1 ml) was added. The reaction mixture was stirred for 2 hours and diethyl ether was added. The precipitates were collected with filtration and dissolved with water. The solution was neutralized with saturated aqueous NaHCO3 and purified by HP-20 resin eluting with isopropanol/water=(0-30%) to give N-[(R)-1-[3-(4-piperidyl)-(Z)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine (0.5 g, 67.8%).

Workup

  1. washthe whole was washed with diethyl ether
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over MgSO4
  4. customevaporated in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (10 ml)
  6. addition4N HCl in ethyl acetate (5.1 ml) was added
  7. stirringThe reaction mixture was stirred for 2 hours
  8. additiondiethyl ether was added
  9. filtrationThe precipitates were collected with filtration
  10. dissolutiondissolved with water
  11. custompurified by HP-20 resin
  12. washeluting with isopropanol/water=(0-30%)

Sources & evidence

ORD record
ord-edabc224436248c5983ff953e9376656
Source dataset
uspto-grants-2002_05
Patent number
US06384028B1

Reaction notes

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