Triethylamine → Methyl 5-chloro-2-(3-phenoxyazetidin-1-yl)nicotinate

HRID 72437

Reaction equation

HRID 72437 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[O:13]([CH:20]1[CH2:23][NH:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>O1CCCC1>[Cl:12][C:9]1[CH:10]=[N:11][C:2]([N:22]2[CH2:21][CH:20]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:23]2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2764318Methyl 2,5-DichloronicotinateHCID 128125013-Phenoxyazetidine

Product 1

HCID 67958085Methyl 5-chloro-2-(3-phenoxyazetidin-1-yl)nicotinateYield 74.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2,5-dichloronicotinate (217 mg, 1.05 mmol) in tetrahydrofuran (5 ml), 3-phenoxyazetidine (D48) (149 mg, 1.05 mmol) and triethylamine (117 mg, 1.16 mmol) were added and the mixture was heated at reflux for 18 hours. The resulting mixture was cooled to room temperature, the precipitates were filtered off and the filtrate was concentrated under vacuo. The residue was dissolved in ethyl acetate (5 ml), washed with water (5 ml) and brine (5 ml), dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate from 30:1 to 20:1. Collected fractions after solvent evaporation afforded the title compound (D75) (250 mg) as a white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 18 hours
  3. filtrationthe precipitates were filtered off
  4. concentrationthe filtrate was concentrated under vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (5 ml)
  6. washwashed with water (5 ml) and brine (5 ml)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by flash chromatography on silica gel eluting with a mixture petroleum ether/ethyl acetate from 30:1 to 20:1
  11. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-1f25136830aa49c1a30b8108e105b5b3
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Linked notes

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