Hydrochloric Acid → (3S,4S)-methyl 4-(3,4-dichlorophenyl)-1-methylpiperidine-3-carboxylate

HRID 227569ノート

反応式

HRID 227569 の反応式
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([Cl:10])[CH:4]=1.[CH3:11][N:12]1[CH2:17][C:16]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][CH2:14][CH2:13]1.Cl>C(OCC)C.C1(C)C=CC=CC=1>[CH3:21][O:20][C:18]([C@H:16]1[C@@H:15]([C:3]2[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([Cl:10])[CH:4]=2)[CH2:14][CH2:13][N:12]([CH3:11])[CH2:17]1)=[O:19].[CH3:21][O:20][C:18]([C@H:16]1[C@H:15]([C:3]2[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([Cl:10])[CH:4]=2)[CH2:14][CH2:13][N:12]([CH3:11])[CH2:17]1)=[O:19]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 2230ArecolineHCID 290134-Bromo-1,2-dichlorobenzeneHCID 5462224Magnesium

生成物 2

HCID 44429174(3S,4S)-methyl 4-(3,4-dichlorophenyl)-1-methylpiperidine-3-carboxylate収率 25%HCID 69593838HCID 69593838、化合物収率 10%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒2 回

反応条件

温度
-40 °C

実験手順

A stirred suspension of magnesium turnings (3.4 g, 142 mmol) in diethyl ether (20 ml) was added a solution of 1-bromo-3,4-dichlorobenzene (29 g, 130 mmol) in diethyl ether (150 ml). The mixture was heated at reflux for 20 minutes and then cooled at −40° C. A solution of arecoline (10 g, 65 mmol) in toluene (100 ml) was added slowly while keeping the internal temperature between −40° C. and −30° C. The reaction mixture was stirred at −20° C. for 6 hours and then added 4 N HCl (50 ml). The phases were then separated and the aqueous phase was added ammonia (aq) until basic pH and extracted with dichloromethane (4×100 ml), dried with magnesium sulfate and evaporated to an oil. The isomers (1) and (2) were separated by column chromatography (petroleum ether, ether, triethylamine 70:25:5) to give 5.0 g (25%) of (1) (mp. 70-75° C.) and 2.0 g (10%) of (2) (oil).

後処理

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 20 minutes
  3. customthe internal temperature between −40° C. and −30° C
  4. customThe phases were then separated
  5. additionthe aqueous phase was added ammonia (aq) until basic pH
  6. extractionextracted with dichloromethane (4×100 ml)
  7. dry with materialdried with magnesium sulfate
  8. customevaporated to an oil
  9. customThe isomers (1) and (2) were separated by column chromatography (petroleum ether, ether, triethylamine 70:25:5)

出典と根拠

ORDレコード
ord-0ffb2c59d59e462282e9e7a31baa14c7
出典データセット
uspto-grants-2009_07
特許番号
US07560562B2

反応ノート

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