2,2,6,6-Tetramethylpiperidine → (R)-6-(3-(4-Bromophenyl)-3-o-tolylpropanoyl)-3-methoxypyridazine 1-oxide

HRID 1527975노트

반응식

HRID 1527975 반응식
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[CH3:16][O:17][C:18]1[N:19]=[N+:20]([O-:24])[CH:21]=[CH:22][CH:23]=1.[Br:25][C:26]1[CH:31]=[CH:30][C:29]([C@H:32]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[CH3:46])[CH2:33][C:34](N(OC)C)=[O:35])=[CH:28][CH:27]=1.[Cl-].[NH4+]>C1COCC1>[Br:25][C:26]1[CH:27]=[CH:28][C:29]([C@H:32]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[CH3:46])[CH2:33][C:34]([C:21]2[N+:20]([O-:24])=[N:19][C:18]([O:17][CH3:16])=[CH:23][CH:22]=2)=[O:35])=[CH:30][CH:31]=1

참가 물질

7

반응물 5

HCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 64013273-Methoxypyridazine 1-oxideHCID 71813344(R)-3-(4-Bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamideHCID 178418339Butyllithium

생성물 1

HCID 86684803(R)-6-(3-(4-Bromophenyl)-3-o-tolylpropanoyl)-3-methoxypyridazine 1-oxide수율 98%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
0 °C

실험 절차

To a solution of 2,2,6,6-tetramethylpiperidine (4.21 g, 19.8 mmol) in THF (130 mL) was added n-butyllithium solution (1.6 M in hexane 12.4 mL, 19.8 mmol) at −30° C., then the solution was stirred at 0° C. for 45 min. After cooling to −70° C. a solution of 3-methoxy-pyridazine-1-oxide (Chem. Pharm. Bull. 1959, 7, 938; 2.50 g, 19.8 mmol) in THF (13 mL) was added dropwise, then a solution of (R)-3-(4-bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamide (example 1, step 5; 1.80 g, 4.95 mmol) in THF (13 mL) was added, maintaining the temperature as close as possible to −70° C. The mixture was stirred for 30 min. Then sat. aq. ammonium chloride solution (30 mL) was added. The reaction mixture was allowed to reach room temperature, then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) afforded the title compound (2.07 g, 98%). White foam, MS: 427.0 [M+H]+.

후처리

  1. additionwas added dropwise
  2. temperaturemaintaining the temperature
  3. customas close as possible to −70° C
  4. stirringThe mixture was stirred for 30 min
  5. customto reach room temperature
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated

출처 및 근거

ORD 기록
ord-35c3861f8b774ce494f1b40aaac2daf0
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090565B2

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