Triethylamine → 1-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]piperidine-4-carboxylic acid ethyl ester

HRID 1716503Notes

Reaction equation

HRID 1716503 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Cl)[N:3]=1.[CH2:10]([O:12][C:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:21](=[S:23])[NH2:22])[CH2:17][CH2:16]1)=[O:14])[CH3:11].[CH2:24](N(CC)CC)C>C(O)C>[CH2:10]([O:12][C:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[S:23][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[N:3]=3)=[CH:24][N:22]=2)[CH2:17][CH2:16]1)=[O:14])[CH3:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 216984342-Bromo-6-(chloromethyl)pyridineHCID 23076419Ethyl 1-carbamothioylpiperidine-4-carboxylate

Product 1

HCID 587071151-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]piperidine-4-carboxylic acid ethyl esterYield 65.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-Bromo-6-chloromethylpyridine obtained in Step 1 of Example 1 (2.90 g, 14.0 mmol) was dissolved in ethanol (30 ml) and 1-thiocarbamoylpiperidine-4-carboxylic acid ethyl ester (3.00 g, 13.9 mmol) obtained in Step 1 was added, and the mixture was heated to reflux for 2 hours. The reaction solution was cooled to room temperature, dimethylormamide dimethylacetal (2.8 ml, 21.1 mmol) and triethylamine (5.9 ml, 42.3 mmol) were added, and the mixture was heated at reflux for 1 hour. After concentration, water was added and the reaction solution was extracted with ethyl acetate and washed with a saturated brine. The organic layer was dried over magnesium sulfate and the residue obtained by vacuum concentration was purified by silica gel chromatography (n-hexane:ethyl acetate=50:50 to 0:100) and the title compound (3.60 g, 65%) was obtained.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 1 hour
  5. concentrationAfter concentration, water
  6. additionwas added
  7. extractionthe reaction solution was extracted with ethyl acetate
  8. washwashed with a saturated brine
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. customthe residue obtained by vacuum concentration
  11. customwas purified by silica gel chromatography (n-hexane:ethyl acetate=50:50 to 0:100)

Sources & evidence

ORD record
ord-873036b610654b578dd31e320414f5d9
Source dataset
uspto-grants-2010_09
Patent number
US07803801B2

Reaction notes

Loading…