1-(Bis(4-fluorophenyl)methyl)piperazine → (S)-1-{4-[Bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-2-cyclohexylamino-4-methyl-pentan-1-one

HRID 990367ノート

反応式

HRID 990367 の反応式
[CH:1]1([NH:7][C@@H:8]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:19][CH:18]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.CO>[F:36][C:33]1[CH:32]=[CH:31][C:30]([CH:23]([C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)[N:24]2[CH2:25][CH2:26][N:27]([C:9](=[O:11])[C@@H:8]([NH:7][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH2:12][CH:13]([CH3:15])[CH3:14])[CH2:28][CH2:29]2)=[CH:35][CH:34]=1

参加物

6

反応物 3

HCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11356330HCID 11356330、化合物

生成物 1

HCID 57173107(S)-1-{4-[Bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-2-cyclohexylamino-4-methyl-pentan-1-one収率 76%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

A suspension of (S)-2-cyclohexylamino-4-methyl-pentanoic acid (0.556 g, 2.62 mmol) and 1-bis(4-fluorophenyl)methyl piperazine (0.378 g, 1.31 mmol) in dry DMF (7 mL) was treated with Triton® B (2.40 mL, 5.28 mmol, 40 weight percent solution in methanol), a clear solution was obtained. The resulting reaction solution was cooled to 0° C. in an ice-water bath. To this solution was added solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.993 g, 2.62 mmol). After stirring at 0° C. for 30 minutes, the cooling bath was removed, and the stirring was continued at ambient temperature for 30 minutes. After this period, the reaction mixture was mixed with 60 mL of diethyl ether and 60 mL of saturated aqueous NaHCO3 solution. White solid which forms was removed by filtration. The two layers of the filtrate were separated; the organic layer was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was purified by flash chromatography (30% EtOAc in hexanes) affording 0.48 g (76%) of the pure titled compound as a white foam: mp 45-54° C. APCI-MS m/z 484.4 (MH+).

後処理

  1. customa clear solution was obtained
  2. customThe resulting reaction solution
  3. customthe cooling bath was removed
  4. waitthe stirring was continued at ambient temperature for 30 minutes
  5. waitAfter this period
  6. additionthe reaction mixture was mixed with 60 mL of diethyl ether and 60 mL of saturated aqueous NaHCO3 solution
  7. customWhite solid which forms was removed by filtration
  8. customThe two layers of the filtrate were separated
  9. washthe organic layer was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL)
  10. dry with materialwas dried over Na2SO4
  11. concentrationThe solution was concentrated in vacuo
  12. customaffording a viscous oil
  13. customThe crude product was purified by flash chromatography (30% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-679bf3247cff44f9ace5588ced8c5fd8
出典データセット
uspto-grants-2002_10
特許番号
US06458781B1

反応ノート

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