Triethylamine → 5-[5-(2-Acetylamino-phenyl)-isoxazol-3-yl]-pentanoic acid ethyl ester

HRID 1616617Notes

Reaction equation

HRID 1616617 reaction equation
C1(N=C=O)C=CC(N=C=O)=CC=1.[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][C:22](=[O:24])[CH3:23])#[CH:14].[CH2:25]([O:27][C:28](=[O:37])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][N+:34]([O-])=[O:35])[CH3:26].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH2:25]([O:27][C:28](=[O:37])[CH2:29][CH2:30][CH2:31][CH2:32][C:33]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22](=[O:24])[CH3:23])[O:35][N:34]=1)[CH3:26]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 610091,4-DiisocyanatobenzeneHCID 10261360N-(2-ethynylphenyl)acetamideHCID 13717120Ethyl 6-nitrohexanoate

Product 1

HCID 591677705-[5-(2-Acetylamino-phenyl)-isoxazol-3-yl]-pentanoic acid ethyl esterYield 116.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add 1,4-phenylenediisocyanate (5.15 g, 32.2 mmol) to a stirred solution of N-(2-ethynyl-phenyl)-acetamide (2.56 g, 16.1 mmol) and 6-nitro-hexanoic acid ethyl ester (4.56 g, 24.1 mmol) in toluene (200 mL, anhydrous) and stir under N2. Add triethylamine (4.5 mL, 32.2 mmol) and heat to reflux under N2 overnight. Filter mixture through a pad of Celite® and rinse with toluene. Concentrate to get 6.2 g yellow oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-60% EtOAc/hexanes to afford the title compound (4.02 g, 76%). Correct regioisomer is confirmed by NOESY. MS (IS) 331 (M+1)+.

Workup

  1. temperatureto reflux under N2 overnight
  2. filtrationFilter mixture through a pad of Celite®
  3. washrinse with toluene
  4. concentrationConcentrate

Sources & evidence

ORD record
ord-ae83905b119e43839c6117c48239beac
Source dataset
uspto-grants-2014_07
Patent number
US08765796B2

Reaction notes

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