Ethyl Acetate → N-(3-fluoro-5-methyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine

HRID 2061504노트

반응식

HRID 2061504 반응식
F[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([F:9])[C:3]=1[N+:10]([O-:12])=[O:11].Cl.Cl.[O:15]1[CH2:20][CH2:19][CH:18]([N:21]2[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]2)[CH2:17][CH2:16]1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)CCC1.[Cl-].[Na+].O>[F:9][C:4]1[C:3]([N+:10]([O-:12])=[O:11])=[C:2]([NH:27][CH:24]2[CH2:23][CH2:22][N:21]([CH:18]3[CH2:19][CH2:20][O:15][CH2:16][CH2:17]3)[CH2:26][CH2:25]2)[CH:7]=[C:6]([CH3:8])[CH:5]=1

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 451567511-(Oxan-4-yl)piperidin-4-amine dihydrochlorideHCID 569244411,3-Difluoro-5-methyl-2-nitrobenzene

생성물 1

HCID 59683262N-(3-fluoro-5-methyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine수율 42.6%

시약·촉매·용매 3

HCID 67553Tetrabutylammonium Iodide촉매HCID 13387N-methyl-2-pyrrolidone용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
50 °C

실험 절차

A mixture of 1,3-difluoro-5-methyl-2-nitrobenzene (1 g), 1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine, dihydrochloride (1.63 g), sodium bicarbonate (1.94 g) and tetrabutyl ammonium iodide (100 mg) in NMP (15 ml) was slowly heated at about 50° C. for 3 hours. After cooling to about 25° C., the reaction mixture was added to ethyl acetate (15 ml) and saturated brine (15 ml). The layers were separated and the aqueous extracted with ethyl acetate (15 ml). The combined ethyl acetate layers were then washed with saturated brine (4×4 ml), dried with 2 g anhydrous sodium sulphate then concentrated under vacuum. The residue was heated with acetonitrile (4 ml) to about 60° C. to give a solution, then cooled to 0 to 5° C. and stirred for 1 hour. The solid was filtered, washed with chilled acetonitrile (2 ml), then dried at 40-45° C. under high vacuum to give the title compound as an orange solid (0.83 g).

후처리

  1. temperatureAfter cooling to about 25° C.
  2. customThe layers were separated
  3. extractionthe aqueous extracted with ethyl acetate (15 ml)
  4. washThe combined ethyl acetate layers were then washed with saturated brine (4×4 ml)
  5. dry with materialdried with 2 g anhydrous sodium sulphate
  6. concentrationthen concentrated under vacuum
  7. temperatureThe residue was heated with acetonitrile (4 ml) to about 60° C.
  8. customto give a solution
  9. temperaturecooled to 0 to 5° C.
  10. filtrationThe solid was filtered
  11. washwashed with chilled acetonitrile (2 ml)
  12. customdried at 40-45° C. under high vacuum

출처 및 근거

ORD 기록
ord-383dbc03b99744c5948605b49cbd4fe3
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08283364B2

반응 노트

불러오는 중…