Chloroiodomethane → 2-Chloro-1-(1-(2,4-dichloro-5-methoxyphenyl)piperidin-4-yl)ethanone

HRID 1804832ノート

反応式

HRID 1804832 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][CH:14]([C:17]([O:19]CC)=O)[CH2:13][CH2:12]1.[Cl:22][CH2:23]I.C[Li]>C1COCC1>[Cl:22][CH2:23][C:17]([CH:14]1[CH2:13][CH2:12][N:11]([C:3]2[CH:4]=[C:5]([O:9][CH3:10])[C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[CH2:16][CH2:15]1)=[O:19]

参加物

5

反応物 3

HCID 11644ChloroiodomethaneHCID 68556359Ethyl 1-(2,4-dichloro-5-methoxyphenyl)piperidine-4-carboxylateHCID 178418348HCID 178418348、化合物

生成物 1

HCID 866397982-Chloro-1-(1-(2,4-dichloro-5-methoxyphenyl)piperidin-4-yl)ethanone収率 102.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-70 °C

実験手順

An oven-dried, 50-mL 2-neck round bottom flask containing a stir bar was fitted with an inert gas inlet and a rubber septum and placed under argon. The flask was charged with ethyl 1-(2,4-dichloro-5-methoxyphenyl)piperidine-4-carboxylate (233 mg, 0.701 mmol) and anhydrous THF (5 mL) and chloroiodomethane (0.102 mL, 1.403 mmol). The mixture was cooled to −70° C. (internal temperature). Once at the prescribed temperature, a solution of methyllithium (0.877 mL of 1.6 M in Et2O, 1.403 mmol) was added dropwise to the mixture via syringe over 5 min. At the conclusion of this period, the mixture was stirred at −70° C. (internal temperature) for 1.5 h and then quenched by adding saturated NH4Cl (2 mL). The pH of the mixture was adjusted to pH 7.5 by careful addition of 2 M HCl. Once at the prescribed pH, the mixture was extracted with EtOAc (25 mL). The aqueous phase was back-extracted with EtOAc and the combined extracts washed with brine, dried (MgSO4) and concentrated on a rotary evaporator to give 2-chloro-1-(1-(2,4-dichloro-5-methoxyphenyl)piperidin-4-yl)ethanone (242 mg). LC-MS: 336.24, [M+H]+; tR=3.84 min (b).

後処理

  1. additionAn oven-dried, 50-mL 2-neck round bottom flask containing a stir bar
  2. customwas fitted with an inert gas inlet
  3. customquenched
  4. additionby adding saturated NH4Cl (2 mL)
  5. additionThe pH of the mixture was adjusted to pH 7.5 by careful addition of 2 M HCl
  6. extractionOnce at the prescribed pH, the mixture was extracted with EtOAc (25 mL)
  7. extractionThe aqueous phase was back-extracted with EtOAc
  8. washthe combined extracts washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated on a rotary evaporator

出典と根拠

ORDレコード
ord-dac81aa92a6146eb9579c083767e09e3
出典データセット
uspto-grants-2013_01
特許番号
US08354432B2

反応ノート

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