Triethylamine → 3-o-Tolyl-isoxazole-4-carboxylic acid ethyl ester

HRID 474363Notes

Reaction equation

HRID 474363 reaction equation
[OH:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH3:10].[CH2:12]([O:14][C:15](=[O:23])[CH:16]=[CH:17]N1CCCC1)[CH3:13].C(N(CC)CC)C>C(OCC)C>[CH2:12]([O:14][C:15]([C:16]1[C:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[CH3:10])=[N:2][O:1][CH:17]=1)=[O:23])[CH3:13]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2748620Ethyl 3-(pyrrolidin-1-yl)acrylateHCID 71403975N-Hydroxy-2-methylbenzene-1-carboximidoyl chloride

Product 1

HCID 666775933-o-Tolyl-isoxazole-4-carboxylic acid ethyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred solution of N-hydroxy-2-methylbenzenecarboximidoyl chloride (2.07 g, 12.2 mmol, 1.0 equiv) in diethyl ether (15 mL) was added a solution of 3-pyrrolidin-1-yl-acrylic acid ethyl ester (prepared according to the procedure described in U.S. Pat. No. 4,187,099) (2.06 g, 12.2 mmol, 1.0 equiv) and triethylamine (1.48 g, 12.2 mmol, 1.0 equiv) in diethyl ether (30 mL) dropwise over 15 minutes. The resultant mixture was stirred at ambient temperature for 16 hours, partitioned between water and diethyl ether and separated. The aqueous phase was extracted with diethyl ether (2×), and the combined ethereal extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Purification by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in cyclohexane) gave 1.32 g (47%) of 3-o-tolyl-isoxazole-4-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ: 9.02 (s, 1H), 7.39-7.34 (m, 1H), 7.32-7.24 (m, 3H), 4.19 (q, 2H), 2.23 (s, 3H), 1.17 (t, 3H).

Workup

  1. customprepared
  2. custompartitioned between water and diethyl ether
  3. customseparated
  4. extractionThe aqueous phase was extracted with diethyl ether (2×)
  5. dry with materialthe combined ethereal extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customPurification by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-799f7462fe024fe7b0fa407bd2d007c8
Source dataset
uspto-grants-2014_01
Patent number
US08637526B2

Reaction notes

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