Hexane → Ethyl 4-propyl-3-(pyridin-2-yl)isoxazole-5-carboxylate

HRID 1951951Notes

Reaction equation

HRID 1951951 reaction equation
[OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.Br[C:12](=[CH:18][CH2:19][CH2:20][CH3:21])[C:13]([O:15][CH2:16][CH3:17])=[O:14].C(N(CC)CC)C.CCCCCC>ClCCl.CN(C)C=O>[CH2:19]([C:18]1[C:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=2)=[N:2][O:1][C:12]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:20][CH3:21]

Participants

7

Reactant 4

HCID 8058HexaneHCID 8471TriethylamineHCID 71332829Ethyl 2-bromohex-2-enoateHCID 135440287N-Hydroxypicolinimidoyl chloride

Product 1

HCID 58062836Ethyl 4-propyl-3-(pyridin-2-yl)isoxazole-5-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a light orange, homogeneous mixture of (Z)—N-hydroxypicolinimidoyl chloride (0.637 g, 4.07 mmol) and ethyl 2-bromohex-2-enoate (0.900 g, 4.07 mmol) in dichloromethane (17 mL) and N,N-dimethylformamide (1 mL) at room temperature was added triethylamine (1.70 mL, 12.2 mmol) slowly over 5 min. The homogeneous reaction mixture was stirred at room temperature over the weekend. The solvent was removed under reduced pressure, and the residue was diluted with ether (100 mL), washed with water (3×75 mL), washed with a saturated aqueous solution of lithium chloride (1×75 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by trituration with hexane, with sonication, afforded a reddish solid and the hexane filtrate containing the desired product and remaining ethyl 2-bromohex-2-enoate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a mixture of ethyl acetate and hexane (0:100-0.5:99.5-1:99) afforded ethyl 4-propyl-3-(pyridin-2-yl)isoxazole-5-carboxylate (0.015 g, 0.058 mmol, 1.5% yield) as a white solid. The compound was had an HPLC ret. time=2.61 min.—Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=261.0. 1H NMR (500 MHz, CDCl3) δ ppm 0.92 (t, J=7.42 Hz, 3H), 1.45 (t, J=7.15 Hz, 3H), 1.55-1.64 (m, 2H), 3.11-3.17 (m, 2H), 4.47 (q, J=7.15 Hz, 2H), 7.37 (dd, J=7.70, 4.95 Hz, 1H), 7.81 (td, J=7.70, 2.20 Hz, 1H), 7.98 (d, J=7.70 Hz, 1H), and 8.72 (d, 1H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with ether (100 mL)
  3. washwashed with water (3×75 mL)
  4. washwashed with a saturated aqueous solution of lithium chloride (1×75 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration under reduced pressure
  7. customfollowed by trituration with hexane, with sonication
  8. customafforded a reddish solid

Sources & evidence

ORD record
ord-21462ef3077d44aa8a88da8be1b4605f
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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