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

HRID 72437

반응식

HRID 72437 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1f25136830aa49c1a30b8108e105b5b3
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828987B2

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