Sodium Iodide → tert-Butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate

HRID 2279561ノート

反応式

HRID 2279561 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[Cl:8].C1OCCOCCOCCOCCOC1.[H-].[Na+].[Na+].[I-].Cl[CH2:32][CH2:33][N:34]([CH2:42][CH2:43]Cl)[C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38].[NH4+].[Cl-]>CN(C=O)C>[C:10]([C:9]1([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:43][CH2:42][N:34]([C:35]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:41])[CH2:33][CH2:32]1)#[N:11]

参加物

8

反応物 6

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 3633615-Crown-5HCID 76690(3,4-Dichlorophenyl)acetonitrileHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

生成物 1

HCID 49760263tert-Butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate収率 68%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a stirred solution of 2-(3,4-dichlorophenyl)acetonitrile (3.50 g, 18.8 mmol, CASRN 3218-49-3) and 15-crown-5 (0.414 g, 1.88 mmol) in DMF (75 mL) at 0° C. under nitrogen was added NaH (1.88 g, 47.0 mmol, 60% mineral oil dispersion) in 2 portions. The reaction mixture was warmed to RT and stirred 35 min then re-cooled to 0° C. NaI (2.82 g, 18.8 mmol) was added followed by a solution of freshly prepared tert-butyl bis-(2-chloroethyl)carbamate (4.56 g, 18.8 mmol) in DMF (10 mL) via syringe. The reaction mixture was warmed to RT and stirred overnight. The reaction mixture was then poured into ice cold sat'd. NH4Cl solution (250 mL) with stirring and the mixture was extracted with EtOAc (2×250 mL). The combined extracts were dried (MgSO4), filtered and concentrated. The crude product was loaded onto a SiO2 column (Biotage 40L) and eluted with hexanes/EtOAc (6/1) to afford 4.54 g (68%) of tert-butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate (356) as an off white solid.

後処理

  1. temperaturethen re-cooled to 0° C
  2. temperatureThe reaction mixture was warmed to RT
  3. stirringstirred overnight
  4. additionThe reaction mixture was then poured into ice cold sat'd
  5. extractionthe mixture was extracted with EtOAc (2×250 mL)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluted with hexanes/EtOAc (6/1)

出典と根拠

ORDレコード
ord-8874d655267d4af8b81e099e585c9895
出典データセット
uspto-grants-2015_09
特許番号
US09133187B2

反応ノート

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