Pyrrolidine → HCID 25417247, compound

HRID 545196Notes

Reaction equation

HRID 545196 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1>CO>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][C:11]2([CH2:12][C:11](=[O:14])[C:10]3[C:16](=[CH:17][CH:18]=[C:19]([NH:15][C:4](=[O:3])[CH3:5])[CH:9]=3)[O:14]2)[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 25417247HCID 25417247, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 24.8 g of 4-methoxyacetanilide, 37.3 mL of acetyl chloride and 250 mL of CH2Cl2 was refluxed until the insoluble solid was dissolved, and then cooled to 0° C. 70.0 g of AlCl3 was gradually added thereto, and then the mixture was heated under reflux for 5 hours. The reaction mixture was poured into 500 mL of water with ice, and stirred for 30 minutes. The resulting precipitate was collected through filtration, washed with water and dried under vacuum to obtain 23.5 g of 5-acetylamino-2-hydroxyacetophenone. 9.96 g of N-Boc-piperidin-4-one, 4.17 mL of pyrrolidine and 75 mL of MeOH were added to 9.66 g of the product, and heated under reflux for 13 hours. The reaction mixture was concentrated, cold MeOH was added to the residue, and the insoluble solid was taken out through filtration and dried under vacuum to obtain 16.3 g of N-{1′-[(tert-butoxy)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide. TFA (43 mL) cooled at 0° C. was gradually added to 16.1 g of the product, and stirred at room temperature for 1 hour. The reaction mixture was concentrated, and TFA still remaining therein was removed through codistillation with toluene added thereto, and 50 mL of Et2O was added to the residue. The resulting insoluble solid was taken out through filtration, washed with Et2O/EtOAc (1/2), and dried under vacuum to obtain N-{4-oxospiro[chroman-2,4′-piperidin]-6-yl}acetamide TFA salt.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 13 hours
  3. concentrationThe reaction mixture was concentrated
  4. additioncold MeOH was added to the residue
  5. filtrationthe insoluble solid was taken out through filtration
  6. customdried under vacuum

Sources & evidence

ORD record
ord-8aa20c1e8b26448f859e1d0c41b9d922
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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