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

HRID 1443711Notes

Reaction equation

HRID 1443711 reaction equation
C1(N=C=O)C=CC(N=C=O)=CC=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([C:22]#[CH:23])[CH:15]=1.[CH2:24]([O:26][C:27](=[O:36])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][N+:33]([O-])=[O:34])[CH3:25].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH2:24]([O:26][C:27](=[O:36])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]1[CH:23]=[C:22]([C:16]2[CH:15]=[C:14]([Cl:13])[CH:19]=[CH:18][C:17]=2[O:20][CH3:21])[O:34][N:33]=1)[CH3:25]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 610091,4-DiisocyanatobenzeneHCID 13717120Ethyl 6-nitrohexanoateHCID 232607034-Chloro-2-ethynyl-1-methoxybenzene

Product 1

HCID 591677645-[5-(5-Chloro-2-methoxy-phenyl)-isoxazol-3-yl]-pentanoic acid ethyl esterYield 64.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add 1,4-phenylenediisocyanate (8.41 g, 52.5 mmol) to a stirred solution of 4-chloro-2-ethynyl-1-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 at room temperature under N2. Add triethylamine (7.3 mL, 52.5 mmol) and heat to reflux under N2 overnight. Filter mixture through a pad of Celite® and rinse with toluene. Concentrate to get 6.6 g of a orange oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-40% EtOAc/hexanes to afford the title compound (4.51 g, 76%). MS (IS) 338 (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-317ea096f36a41729f7ebe3d44984a57
Source dataset
uspto-grants-2010_02
Patent number
US07662771B2

Reaction notes

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