Dimethyl nitromalonate → Methyl 4-cyclopropyl-5-phenylisoxazole-3-carboxylate

HRID 1804465

Reaction equation

HRID 1804465 reaction equation
[CH:1]1([C:4]#[C:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[N+:12]([CH:15](C(OC)=O)[C:16]([O:18][CH3:19])=[O:17])([O-])=[O:13]>C1(C)C=C(C)C=C(C)C=1>[CH:1]1([C:4]2[C:15]([C:16]([O:18][CH3:19])=[O:17])=[N:12][O:13][C:5]=2[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 226085Dimethyl nitromalonateHCID 10888024(Cyclopropylethynyl)benzene

Product 1

HCID 58537215Methyl 4-cyclopropyl-5-phenylisoxazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 7947MesityleneSolvent

Procedure

A solution of (cyclopropylethynyl)benzene (300 mg, 2.110 mmol) and dimethyl nitromalonate (0.854 mL, 6.33 mmol) in mesitylene (4 mL) was heated to 150° C. for 16 h. The reaction mixture was concentrated to yield a crude product which was purified by silica gel chromatography with hexanes/ethyl acetate (10/1) to yield methyl 4-cyclopropyl-5-phenylisoxazole-3-carboxylate. The compound was re-purified by preparative HPLC [Column: PHENOMENEX® S10 30×100 mm; Gradient time: 10 min; Flow rate=40 ml/min; Solvent A=10% MeOH−90% Water−0.1% TFA; Solvent B=90% MeOH−10% water−0.1% TFA; Start % B=20; Final % B=100] to yield methyl 4-cyclopropyl-5-phenylisoxazole-3-carboxylate (170 mg). The compound had an HPLC ret. time=2.77 min.−Column. YMC S5 COMBISCREEN® 4.6×50 mm; Gradient time: 4 min; Flow rate=4 ml/min; Solvent A=10% MeOH−90% Water−0.2% H3PO4; Solvent B=90% MeOH−10% water−0.2% H3PO4; Start % B=0; Final % B=100. LC-MS: M+1=244+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto yield a crude product which
  3. customwas purified by silica gel chromatography with hexanes/ethyl acetate (10/1)

Sources & evidence

ORD record
ord-14c5b1ff1de04fc18edcaea083ae3854
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Linked notes

Loading…