Ethyl 2-chloroacetoacetate → HCID 86693518, compound

HRID 575456Notes

Reaction equation

HRID 575456 reaction equation
C([O-])(=O)C.[Na+].[CH2:6]([O:8][C:9](=[O:15])[CH:10]([Cl:14])C(=O)C)[CH3:7].[CH2:16]([O:20][C:21]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:22]=1[NH2:23])[CH2:17][C:18]#[CH:19].[N:29]([O-])=O.[Na+]>C(O)C.Cl.O1CCCC1.O>[CH2:16]([O:20][C:21]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:22]=1[NH:23][N:29]=[C:10]([Cl:14])[C:9]([O:8][CH2:6][CH3:7])=[O:15])[CH2:17][C:18]#[CH:19]

Participants

9

Reactant 4

HCID 11858Ethyl 2-chloroacetoacetateHCID 517045Sodium AcetateHCID 23668193Sodium NitriteHCID 86693519HCID 86693519, compound

Product 1

HCID 86693518HCID 86693518, compoundYield 96.2%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of sodium acetate (1.29 g, 15.7 mmol) and 2-chloro-3-oxo-butyric acid ethyl ester (1.4 ml, 10.0 mmol) in ethanol (125 ml) was stirred at room temperature for 1 hours and then cooled to 0° C. In a separate flask a mixture of 2-(but-3-yn-1-yloxy)-5-iodoaniline (2.81 g, 9.79 mmol) in hydrochloric acid (6 M, 6.8 ml) and tetrahydrofuran (2 ml) was cooled to 0° C. before a solution of sodium nitrite (685 mg, 9.79 mmol) in water (−10 ml) was added slowly. After stirring for 30 minutes in the cold the diazonium salt mixture was washed into the ethanol solution with a small amount of water. The resulting solution was stirred for one hour at 0° C. before being added to water (600 ml) and ethyl acetate (200 ml). After separation the aqueous layer was further extracted with ethyl acetate (2×200 ml) and the combined extracts were washed with brine (200 ml), dried over MgSO4, filtered and concentrated. The residue was co-evaporated with ethyl acetate (2×) to give 3.96 g (96%) of the title compound as a crystalline solid. 1H NMR (500 MHz, CDCl3) 8 ppm 1.43 (3H, t, J=7.17 Hz), 2.06 (1H, t, J=2.67 Hz), 2.73 (2H, td, J=6.49, 2.59 Hz), 4.17 (2H, t, J=6.48 Hz), 4.41 (2H, q, J=7.17 Hz), 6.64 (1H, d, J=8.39 Hz), 7.27 (1H, dd, J=8.70, 2.14 Hz), 7.82 (1H, d, J=2.14 Hz), 8.81 (1H, s); M+23=443.

Workup

  1. temperaturecooled to 0° C
  2. additionwas added slowly
  3. washwas washed into the ethanol solution with a small amount of water
  4. stirringThe resulting solution was stirred for one hour at 0° C.
  5. additionbefore being added to water (600 ml) and ethyl acetate (200 ml)
  6. customAfter separation the aqueous layer
  7. extractionwas further extracted with ethyl acetate (2×200 ml)
  8. washthe combined extracts were washed with brine (200 ml)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-eea3a07228494991abc2ec004ce6c9c9
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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