Triethylamine → Ethyl 5-phenylisoxazole-3-carboxylate

HRID 1506282Notes

Reaction equation

HRID 1506282 reaction equation
Cl/[C:2](=[N:8]\[OH:9])/[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)#[CH:11].C(N(CC)CC)C>CCOCC>[C:12]1([C:10]2[O:9][N:8]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:11]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 95760052-Chloro-2-hydroxyiminoacetic acid ethyl ester

Product 1

HCID 571142Ethyl 5-phenylisoxazole-3-carboxylateYield 70.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a mixture of (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (3.03 g, 20 mmol) and ethynylbenzene (4.39 mL, 40 mmol) in ether (80 mL) at room temperature was added a solution of triethylamine (5.58 mL, 40.0 mmol) in ether (20 mL) dropwise over 60 minutes. The reaction mixture was stirred for 2 h at room temperature and filtered. The filtrate was concentrated to give an yellow oil which was purified by flash silica gel chromatography using a mixture of ethyl acetate in hexane (0-12%) to afford ethyl 5-phenylisoxazole-3-carboxylate (3.06 g, 14.09 mmol, 70% yield) as a white solid. The compound had an HPLC retention time=2.99 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)=218.12. 1H NMR (400 MHz, CDCl3) δ ppm 1.45 (t, J=7.3 Hz, 3H), 4.48 (q, J=7.3, 2H), 6.93 (s, 1H), 7.45-7.53 (m, 3H), and 7.77-7.85 (m, 2H).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. customto give an yellow oil which
  4. customwas purified by flash silica gel chromatography
  5. additiona mixture of ethyl acetate in hexane (0-12%)

Sources & evidence

ORD record
ord-dc608332db6c4a86b48068661c1c219b
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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