Triethylamine → Dimethyl 3-phenyl-4,5-isoxazoledicarboxylate

HRID 1804490Notes

Reaction equation

HRID 1804490 reaction equation
[OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]([O:19][CH3:20])(=[O:18])[C:12]#[C:13][C:14]([O:16][CH3:17])=[O:15].CCN(CC)CC>CCOCC>[C:4]1([C:3]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([C:11]([O:19][CH3:20])=[O:18])[O:1][N:2]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12980Dimethyl acetylenedicarboxylateHCID 5706359Alpha-chlorobenzaldoxime

Product 1

HCID 608690Dimethyl 3-phenyl-4,5-isoxazoledicarboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of (Z)-N-hydroxybenzimidoyl chloride (467 mg, 3 mmol) and dimethyl but-2-ynedioate (0.374 mL, 3.00 mmol) in Et2O (10 mL) at rt was added dropwise over 5 minutes Et3N (0.460 mL, 3.30 mmol). The reaction mixture became a thick suspension and was stirred at rt for 2 hr. After filtration, the filtrate was concentrated to an oil that was chromatographed on a 24 gm Isco silica gel cartridge, eluting with a 0-25% EtOAc/Hex gradient. The pure fractions were concentrated to afford dimethyl 3-phenylisoxazole-4,5-dicarboxylate (780 mg, 2.99 mmol, 100% yield) as a colorless oil. HPLC retention time=2.86 minutes (YMC Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=262.15. 1H NMR (500 MHz, CDCl3) d ppm 3.91 (s, 2H) 4.02 (s, 2H) 7.46-7.53 (m, 2H) 7.69 (d, J=6.6 Hz, 1H).

Workup

  1. filtrationAfter filtration
  2. concentrationthe filtrate was concentrated to an oil that
  3. customwas chromatographed on a 24 gm Isco silica gel cartridge
  4. washeluting with a 0-25% EtOAc/Hex gradient
  5. concentrationThe pure fractions were concentrated

Sources & evidence

ORD record
ord-fb912a77028f40168227553ca5e3a061
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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