Morpholine → 2-Chloro-5-(morpholin-4-yl)aniline

HRID 1431575노트

반응식

HRID 1431575 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:9])=[C:6]([CH:8]=1)[NH2:7].[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:9][C:5]1[CH:4]=[CH:3][C:2]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:8][C:6]=1[NH2:7]

참가 물질

8

반응물 4

HCID 8083MorpholineHCID 38307312-Chloro-5-bromoanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

생성물 1

HCID 176073522-Chloro-5-(morpholin-4-yl)aniline

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

A mixture of 5-bromo-2-chloroaniline (2.0 g, 9.74 mmol), morpholine (4.3 mL, 49 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (0.37 g, 0.79 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.37 g, 0.4 mmol) in dry THF (20 mL) was degassed by nitrogen. To this mixture was added 1.0M lithium bis(trimethylsilyl)amide in THF (54 mL) dropwise, and the resulting reaction was heated to 60° C. After 2 h, the reaction was cooled to rt then cond under reduced pressure to ˜5 mL. After pouring into water, the mixture was extracted twice with EtOAc and twice with DCM. After the combined organic layers were dried over anhydrous magnesium sulfate, filtration, and concentration, the residue was purified on silica gel (0-30% EtOAc in hexanes) to yield 2-chloro-5-morpholinoaniline. 1H NMR (400 MHz, CDCl3) δ ppm 7.19 (1H, m), 6.41 (2H, m), 4.00 (2H, br. s.), 3.93 (4H, m), 3.22 (4H, m).

후처리

  1. customwas degassed by nitrogen
  2. additionTo this mixture was added 1.0M lithium bis(trimethylsilyl)amide in THF (54 mL) dropwise
  3. customthe resulting reaction
  4. temperaturethe reaction was cooled to rt
  5. extractionthe mixture was extracted twice with EtOAc and twice with DCM
  6. dry with materialAfter the combined organic layers were dried over anhydrous magnesium sulfate, filtration, and concentration
  7. customthe residue was purified on silica gel (0-30% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-a531dddb1390436b948788f58208e71f
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

반응 노트

불러오는 중…