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

HRID 72437

反応式

HRID 72437 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1f25136830aa49c1a30b8108e105b5b3
出典データセット
uspto-grants-2014_09
特許番号
US08828987B2

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