2-Methyl-4-methoxyaniline → 1-(4-Methoxy-2-methylphenyl)pyrrolidin-2-one

HRID 32789

반응식

HRID 32789 반응식
CCN(CC)CC.[CH3:8][O:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[C:12]([CH3:17])[CH:11]=1.Cl[CH2:19][CH2:20][CH2:21][C:22](Cl)=[O:23].CC([O-])(C)C.[K+]>C1COCC1.O>[CH3:8][O:9][C:10]1[CH:16]=[CH:15][C:13]([N:14]2[CH2:19][CH2:20][CH2:21][C:22]2=[O:23])=[C:12]([CH3:17])[CH:11]=1

참가 물질

7

반응물 4

HCID 76102-Methyl-4-methoxyanilineHCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 23665647Potassium tert-butoxide

생성물 1

HCID 251558151-(4-Methoxy-2-methylphenyl)pyrrolidin-2-one수율 92%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
0 °C

실험 절차

To a solution of Et3N (156 mL, 1 eq) and 4-methoxy-2-methylaniline (150 g, 1.09 mole) in anh. THF (2.4 L), in a 10 L reaction vessel, at 0° C., under N2, was added dropwise a solution of 4-chlorobutyryl chloride (126 mL, 1 eq) in anh. THF (480 mL). The internal temperature was maintained at circa 10° C. and the reaction mixture was stirred for 1.5 hr. It was cooled down to 0° C. and KOt-Bu 1M/THF (2.64 L, 2.4 eq) was added dropwise over a period of 1.5 hr, keeping the internal temperature <10° C. The reaction mixture was stirred at that temperature for 30 min. Water (1.5 L) was then added slowly (20 min) and the phases were separated. The organic layer was treated with conc. HCl (250 mL) and water (1.26 L) and the phases were separated. The combined aqueous layers were extracted with EtOAc (2.6 L) and the combined organic layers were washed with brine (2 L). The solvent was evaporated and the residue purified by flash chromatography (Biotage 150, EtOAc/cHex 8:2) to give the title compound as a pale brown solid (206 g, 92%).

후처리

  1. temperatureThe internal temperature was maintained at circa 10° C.
  2. customthe internal temperature <10° C
  3. stirringThe reaction mixture was stirred at that temperature for 30 min
  4. customthe phases were separated
  5. additionThe organic layer was treated with conc. HCl (250 mL) and water (1.26 L)
  6. customthe phases were separated
  7. extractionThe combined aqueous layers were extracted with EtOAc (2.6 L)
  8. washthe combined organic layers were washed with brine (2 L)
  9. customThe solvent was evaporated
  10. customthe residue purified by flash chromatography (Biotage 150, EtOAc/cHex 8:2)

출처 및 근거

ORD 기록
ord-c95ed795a57844d4aa65235732a31cb7
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427630B2

연결된 노트

불러오는 중…