4-Methylmorpholine → 4-(4-Chlorophenyl)-4-dimethylcarbamoyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 409563ノート

反応式

HRID 409563 の反応式
[C:1]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:24][N:25]1CCOC[CH2:26]1.C1C=CC2N(O)N=NC=2C=1.Cl.CNC.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CN(C=O)C>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)([C:14](=[O:15])[N:25]([CH3:26])[CH3:24])[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

参加物

8

反応物 6

HCID 79724-MethylmorpholineHCID 10473Dimethylamine, hydrochlorideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248288571-(Tert-butoxycarbonyl)-4-(4-chlorophenyl)piperidine-4-carboxylic acid

生成物 1

HCID 596621944-(4-Chlorophenyl)-4-dimethylcarbamoyl-piperidine-1-carboxylic acid tert-butyl ester収率 94%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

N-Boc-4-(4-chlorophenyl)-4-piperidine carboxylic acid Compound 2-1 (5.96 g, 18 mmol, Arch Chemical) was dissolved in DMF (175 mL) and chilled in an ice bath temp. To the solution was added N-methylmorpholine (5.76 mL, 53 mmol), HOBt (1.18 g, 8.8 mmol), dimethylamine hydrochloride (1.41 g, 18 mmol), and HBTU (10.0 g, 26 mmol). The solution was allowed to warm overnight to rt, poured into 1N sodium hydroxide solution (100 mL), and extracted with EtOAc (3×75 mL). The combined organic layers were washed with 1N NaOH (2×), 1N hydrochloric acid solution (2×), and brine (3×); and dried over Na2SO4 and concentrated to give Compound 2-2 (6.1 g, 17 mmol, 94%) as a white solid. 1H NMR (300 MHz, CDCl3,) δ 7.32 (d, J=9 Hz, 2H), 7.17 (d, J=9 Hz, 2H), 4.2-3.8 (br m, 2H), 3.0-2.6 (br m, 2H), 2.96 (s, 3H), 2.80 (s, 3H), 2.25 (m, 2H), 2.1-1.7 (br m, 2H), 1.45 (s, 9H).

後処理

  1. temperaturechilled in an ice bath temp
  2. temperatureto warm overnight to rt
  3. extractionextracted with EtOAc (3×75 mL)
  4. washThe combined organic layers were washed with 1N NaOH (2×), 1N hydrochloric acid solution (2×), and brine (3×)
  5. dry with materialand dried over Na2SO4
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-264bf82e45024151afc10a4bafeb4e79
出典データセット
uspto-grants-2014_06
特許番号
US08759342B2

反応ノート

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