4-Chlorotoluene → 4-(p-Tolyl)morpholine

HRID 1778641노트

반응식

HRID 1778641 반응식
CC(C)([O-])C.[Na+].P.Cl[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1>C(#N)C.C(Cl)Cl.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].O1CCOCC1>[C:12]1([CH3:15])[CH:13]=[CH:14][C:9]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[CH:10][CH:11]=1

참가 물질

9

반응물 4

HCID 78104-ChlorotolueneHCID 8083MorpholineHCID 24404PhosphineHCID 23676156Sodium t-butoxide

생성물 1

HCID 7662554-(p-Tolyl)morpholine

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

In a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar was charged with sodium tert-butoxide (56.9 mg, 0.592 mmol, 1.5 equivalents), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) (3.62 mg, 0.00395 mmol, 0.01 equivalents), phosphine ligand (0.00869 mmol, 0.022 equivalents) and dioxane (0.79 mL). To the slurry was added 4-chlorotoluene (47 μL, 0.395 mmol, 1 equivalents) and morpholine (42 μL, 0.474 mmol, 1.2 equivalents). The vial was sealed with a crimp top and stirred at 100° C. After 14 hours, the vial was removed from the heating block, cooled to room temperature and brought out of the glovebox. To assay the crude reaction, an aliquot (7 μL) was taken and diluted in acetonitrile (1.5 mL), then injected onto an HPLC instrument. For isolation purposes, the reaction solution was worked up by diluting with CH2Cl2 (2 mL) and filtering into a round-bottom flask. The vial was rinsed with CH2Cl2 (5 mL), followed by washing of the filter cake CH2Cl2 (2 mL). The volatiles were removed on a rotary evaporator and the crude concentrate was purified by silica gel column chromatography (25 g silica gel, 85:15 heptane:ethyl acetate). The purified product was isolated as a beige solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.10 (d, J=8.2 Hz, 1H), 6.88-6.81 (m, 2H), 3.87 (dd, J=5.7, 3.9 Hz, 4H). 3.15-3.09 (m, 4H), 2.29 (s, 3H).

후처리

  1. customIn a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar
  2. customThe vial was sealed with a crimp top
  3. customthe vial was removed from the heating block
  4. temperaturecooled to room temperature
  5. customreaction
  6. filtrationfiltering into a round-bottom flask
  7. washThe vial was rinsed with CH2Cl2 (5 mL)
  8. washby washing of the filter cake CH2Cl2 (2 mL)
  9. customThe volatiles were removed on a rotary evaporator
  10. concentrationthe crude concentrate
  11. customwas purified by silica gel column chromatography (25 g silica gel, 85:15 heptane:ethyl acetate)
  12. customThe purified product was isolated as a beige solid

출처 및 근거

ORD 기록
ord-0edda25c9c9846a29bdef4ff3135a69c
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266913B2

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