Ethyl Acetate → HCID 67983767, compound

HRID 1748185Notes

Reaction equation

HRID 1748185 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:7]1([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH3:21])[C:11]=2[C:22](OC)=[O:23])[CH2:9][CH2:8]1.C(OCC)(=O)C.[OH-].[Na+]>O1CCCC1.O>[CH:7]1([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH3:21])[C:11]=2[CH2:22][OH:23])[CH2:9][CH2:8]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 67983659HCID 67983659, compound

Product 1

HCID 67983767HCID 67983767, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Lithium aluminum hydride (1M in tetrahydrofuran, 29 mL, 29 mmol, 2.5 eq) was added to a dry three-necked flask filled with nitrogen and cooled to 0° C. Methyl 5-cyclopropyl-3-(o-tolyl)isoxazole-4-carboxylate (3.02 g, 11.7 mmol) was dissolved in tetrahydrofuran (40 mL) and added dropwise to the flask, ensuring that the internal temperature remained below −10° C. The mixture was stirred for an hour, then ethyl acetate (1.3 mL) was added dropwise, keeping the temperature below 0° C. followed by water (1.3 mL), taking care that the mixture was vigorously stirring at all times. Sodium hydroxide solution (3.9 mL, 15% solution by weight) was added dropwise and the mixture stirred vigorously for a further 30 minutes, warming up to RT. The mixture was filtered through a CELITE® pad, which was washed with ethyl acetate (120 mL). The organics were washed with water (100 mL) and brine (75 mL) then dried over magnesium sulfate and concentrated under vacuum and purified by column chromatography (SiO2, linear gradient, 0-100% ethyl acetate in hexanes) to afford the desired product. 1H-NMR (MeOH-d4, 400 MHz) δ 7.41-7.26 (m, 4H), 4.36 (s, 2H), 2.34-2.27 (m, 1H), 2.26 (s, 3H), 1.19-1.15 (m, 4H), MS m/z 230.0 (M+1).

Workup

  1. additionfilled with nitrogen
  2. additionadded dropwise to the flask
  3. customremained below −10° C
  4. customthe temperature below 0° C.
  5. stirringwas vigorously stirring at all times
  6. stirringthe mixture stirred vigorously for a further 30 minutes
  7. temperaturewarming up to RT
  8. filtrationThe mixture was filtered through a CELITE® pad, which
  9. washwas washed with ethyl acetate (120 mL)
  10. washThe organics were washed with water (100 mL) and brine (75 mL)
  11. dry with materialthen dried over magnesium sulfate
  12. concentrationconcentrated under vacuum
  13. custompurified by column chromatography (SiO2, linear gradient, 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f83cc42ac83f4e429ca789f938a8ac81
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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