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

HRID 447792ノート

反応式

HRID 447792 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 13387N-methyl-2-pyrrolidone溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c07866e3d5604193ada526fbbf9447f8
出典データセット
uspto-grants-2013_07
特許番号
US08481566B2

反応ノート

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