Citric Acid → ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzofuranyl)acrylate

HRID 53960

Reaction equation

HRID 53960 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[C:28]([C:30]1[CH:31]=[CH:32][C:33]2[O:37][C:36]([CH2:38][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:35][C:34]=2[CH:58]=1)#[N:29].[H-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C1(C)C=CC=CC=1.C(OCC)(=O)C.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[CH:15]=[CH:16][C:17]([C:20](=[CH:38][C:36]3[O:37][C:33]4[CH:32]=[CH:31][C:30]([C:28]#[N:29])=[CH:58][C:34]=4[CH:35]=3)[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:18][CH:19]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 10316641Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-2-oxoacetateHCID 21844326(5-Cyano-2-benzofuranyl)methyltriphenylphosphonium chloride

Product 1

HCID 57233554ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzofuranyl)acrylateYield 71.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 21584019Toluene ethylacetateSolvent

Procedure

3.12 g of ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-2-oxoacetate was dissolved in 100 ml of tetrahydrofuran, followed by the addition of 4.65 g of (5-cyano-2-benzofuranyl)methyltriphenylphosphonium chloride. To the thus prepared solution was added 400 mg of 60% sodium hydride. With stirring, to the resulting mixture was added dropwise 3 ml of ethanol, followed by stirring at room temperature for 1 hour. The resulting reaction solution was neutralized with 10% citric acid solution, extracted with ethyl acetate, and then dried to distill off the solvent. Thereafter, the residue thus obtained was subjected to silica gel column chromatography using a toluene/ethyl acetate mixture as an elution solvent, thereby obtaining 3.1 g of ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzofuranyl)acrylate in the form of viscous oil as a mixture of E and Z forms. A portion of the thus obtained compound was separated into E and Z forms.

Workup

  1. stirringby stirring at room temperature for 1 hour
  2. customThe resulting reaction solution
  3. extractionextracted with ethyl acetate
  4. customdried
  5. distillationto distill off the solvent
  6. customThereafter, the residue thus obtained

Sources & evidence

ORD record
ord-0a27aad3018848dcaf859c6a17fa36c3
Source dataset
uspto-grants-1997_04
Patent number
US05620991

Linked notes

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