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

HRID 1616594Notes

Reaction equation

HRID 1616594 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[O:21][CH3:22])#[CH:14].[CH2:23]([O:25][C:26](=[O:35])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][N+:32]([O-])=[O:33])[CH3:24].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH2:23]([O:25][C:26](=[O:35])[CH2:27][CH2:28][CH2:29][CH2:30][C:31]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][CH3:22])[O:33][N:32]=1)[CH3:24]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 610091,4-DiisocyanatobenzeneHCID 5829121-Ethynyl-2-methoxybenzeneHCID 13717120Ethyl 6-nitrohexanoate

Product 1

HCID 591677545-[5-(2-Methoxy-phenyl)-isoxazol-3-yl]-pentanoic acid ethyl esterYield 97.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add 1,4-phenylenediisocyanate (14.5 g, 90.8 mmol) to a stirred solution of 1-ethynyl-2-methoxy-benzene (4.0 g, 30.3 mmol) and 6-nitro-hexanoic acid ethyl ester (8.6 g, 45.4 mmol) in toluene (300 mL, anhydrous) and stir under N2. Add triethylamine (12.7 mL, 90.8 mmol) and heat to reflux under N2. After 2.5 hours, filter mixture through a pad of Celite® and rinse with toluene. Concentrate to get 9 grams of a orange oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-20% EtOAc/hexanes to afford the title compound (14.0 g, 74%).

Workup

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

Sources & evidence

ORD record
ord-8fdedc1bb2fc4f1b82ec728eb9fbd26e
Source dataset
uspto-grants-2014_07
Patent number
US08765796B2

Reaction notes

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