Tributylstannane → 4-(2-(4-Methylphenylsulfanyl)phenyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 856906ノート

反応式

HRID 856906 の反応式
ClC(=O)C(OC)=O.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[S:28][C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)(O)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].CCCC[SnH](CCCC)CCCC.CC(N=NC(C#N)(C)C)(C#N)C>CN(C)C1C=CN=CC=1.C(OCC)(=O)C.C(Cl)(Cl)Cl.CC#N>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[S:28][C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]

参加物

9

反応物 4

HCID 5948TributylstannaneHCID 6547AzobisisobutyronitrileHCID 79846Methyl chloroglyoxylateHCID 218649151-Tert-butoxycarbonyl-4-[2-(4-methylphenylsulfanyl)phenyl]piperidin-4-ol

生成物 1

HCID 685473954-(2-(4-Methylphenylsulfanyl)phenyl)-piperidine-1-carboxylic acid tert-butyl ester収率 67.4%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 6212Chloroform溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Methyl Chloro-oxo-acetate (1.37 g, 11.25 mmol) was added to a stirred solution of 1-tert-butoxycarbonyl-4-[2-(4-methylphenylsulfanyl)phenyl]piperidin-4-ol (3.00 g, 7.5 mmol) and 4-(dimethylamino)pyridine (1.65 g, 13.5 mmol) in a mixture of dry CH3CN (24 ml) and CHCl3 (12 mL) at 0° C. under argon. The reaction mixture was allowed to reach room temperature and then stirred 2 h. Ethyl acetate (140 mL) was added and some salts were removed by filtration through celite. The organic phase was washed with sat. NaHCO3 (140 ml), brine (140 mL) and dried (MgSO4). The solvents were evaporated in vacuo and the crude material was dried in vacuo. This material was dissolved in dry toluene (48 mL) under argon. Bu3SnH (3.27 g, 11.25 mmol) and AIBN (0.31 g, 1.88 mmol) were added. The solution was stirred under argon at 90° C. for 2.5 h. The solvent was evaporated in vacuo, and the crude material was purified by flash chromatography on silica gel (eluent: a stepwise gradient of ethylacetate in heptane from 10:90 to 20:80) to produce 4-(2-(4-methylphenylsulfanyl)phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a clear oil (1.94 g, 67%). This oil was dissolved in MeOH (9.2 mL) and HCl in diethylether (2.0 M) was added at 0° C. The reaction mixture was allowed to warm to room temperature and stirred overnight. The target compound was collected as its hydrochloride. M.p 229–231° C. Calculated for C18H21NS.HCl: C, 67.58; H, 6.63; N, 4.38. Found: C, 67.33; H, 6.97; N, 4.31. LC/MS (m/z) 284 (MH+); RT=2.12; purity (UV, ELSD): 96%, 100%; yield: 0.26 g (46%).

後処理

  1. customto reach room temperature
  2. customsome salts were removed by filtration through celite
  3. washThe organic phase was washed with sat. NaHCO3 (140 ml), brine (140 mL)
  4. dry with materialdried (MgSO4)
  5. customThe solvents were evaporated in vacuo
  6. dry with materialthe crude material was dried in vacuo
  7. dissolutionThis material was dissolved in dry toluene (48 mL) under argon
  8. stirringThe solution was stirred under argon at 90° C. for 2.5 h
  9. customThe solvent was evaporated in vacuo
  10. customthe crude material was purified by flash chromatography on silica gel (eluent

出典と根拠

ORDレコード
ord-4a0a4b309f65450d8fc0d9766131851d
出典データセット
uspto-grants-2006_12
特許番号
US07144884B2

反応ノート

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