Ethyl 4-chloroacetoacetate → HCID 25269403, compound

HRID 1971253Notes

Reaction equation

HRID 1971253 reaction equation
[C:1]12([CH2:11][NH:12][C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[N:16]=3)=[O:14])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH2:22]([O:24][C:25](=[O:31])[CH2:26][C:27](=O)[CH2:28]Cl)[CH3:23]>CCO>[CH2:22]([O:24][C:25](=[O:31])[CH2:26][C:27]1[N:21]=[C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([C:13](=[O:14])[NH:12][CH2:11][C:1]34[CH2:2][CH:3]5[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]5)[CH2:10]3)[CH2:8]4)[N:16]2[CH:28]=1)[CH3:23]

Participants

4

Reactant 2

HCID 69484Ethyl 4-chloroacetoacetateHCID 59451918HCID 59451918, compound

Product 1

HCID 25269403HCID 25269403, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of N-(1-adamantylmethyl)-6-aminopyridine-2-carboxamide (1.4 g, 4.9 mmol) and 4-chloro-3-oxo-butyric acid ethyl ester (808 mg, 4.9 mmol) in EtOH (20 mL) is heated under reflux for 20 h. After cooling to RT, the solvent is removed in vacuo. The residue is partitioned between EtOAc and saturated aqueous sodium carbonate. The organic layer is separated, and the aqueous layer is back extracted with EtOAc. The combined organic layers are washed with water and brine, dried over sodium sulfate, and concentrated. The brown residue is purified by re-crystallization from 2% MeOH in CH2Cl2 to give the title compound. 1H-NMR (δ, ppm, CDCl3 as internal standard): 8.39 (s, 1H), 7.71 (d, 1H), 7.16 (t, 1H), 7.06 (d, 1H), 6.22 (m, 1H), 4.20 (q, 2H), 3.87 (s, 2H), 3.20 (d, 2H), 2.02 (m, 3H), 1.78-1.58 (m, 12H), 1.28 (t, 3H).

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 20 h
  3. customthe solvent is removed in vacuo
  4. customThe residue is partitioned between EtOAc and saturated aqueous sodium carbonate
  5. customThe organic layer is separated
  6. extractionthe aqueous layer is back extracted with EtOAc
  7. washThe combined organic layers are washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe brown residue is purified by re-crystallization from 2% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-a5c330316bfe4498b7bf33dce6acba5a
Source dataset
uspto-grants-2013_04
Patent number
US08431593B2

Reaction notes

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