Triethylamine → 1,1-Dimethylethyl 4-[(4-methyl-1-piperazinyl)carbonyl]-1-piperidinecarboxylate

HRID 446853ノート

反応式

HRID 446853 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:48][N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]([N:52]2[CH2:53][CH2:54][N:49]([CH3:48])[CH2:50][CH2:51]2)=[O:16])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 8471Triethylamine2 回HCID 531671-MethylpiperazineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

生成物 1

HCID 39614341,1-Dimethylethyl 4-[(4-methyl-1-piperazinyl)carbonyl]-1-piperidinecarboxylate収率 87%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

The solution of 1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid (Aldrich) (21.88 g, 95.4 mmol), triethylamine (13.3 mL, 95.4 mmol) and HBTU [O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (Advanced Chem. Tech.)] (38.36 g, 101.0 mmol) in dry dimethylformamide (100 mL) was stirred at room temperature for five minutes before N-methyl-piperazine (10.6 mL, 95.5 mmol) was added. The pH of the reaction mixture was adjusted to 8 by the addition of triethylamine, the so obtained mixture was stirred at room temperature overnight, then concentrated in vacuo. The residue was treated with saturated sodium hydrogencarbonate solution (350 mL), extracted with ethyl acetate (3×250 mL), the combined organic layers were washed with saturated sodium hydrogencarbonate solution, water and brine, dried over sodium sulfate, filtered and concentrated. The residue was submitted to column chromatography using Kieselgel 60 (0.040-0.063 mm) (Merck) as adsorbent, and chloroform:methanol=9:1 as eluent to yield 25.8 g (87%) of the title compound as an oil.

後処理

  1. additionwas added
  2. concentrationconcentrated in vacuo
  3. additionThe residue was treated with saturated sodium hydrogencarbonate solution (350 mL)
  4. extractionextracted with ethyl acetate (3×250 mL)
  5. washthe combined organic layers were washed with saturated sodium hydrogencarbonate solution, water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-c48d041af8f843bfa03e9d15fef23008
出典データセット
uspto-grants-2013_07
特許番号
US08481527B2

反応ノート

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