Hydrochloric Acid → Tert-butyl 4-(3,4-difluorobenzyl)-4-hydroxypiperidine-1-carboxylate

HRID 538479ノート

反応式

HRID 538479 の反応式
[Mg].BrCCBr.[F:6][C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=1[F:15])[CH2:10]Br.[O:16]=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.Cl.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(OCC)C.C1COCC1>[F:6][C:7]1[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=1[F:15])[CH2:10][C:17]1([OH:16])[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:21][CH2:22]1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 78391,2-DibromoethaneHCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5462224MagnesiumHCID 9855836Potassium sodium tartarate

生成物 1

HCID 86680862Tert-butyl 4-(3,4-difluorobenzyl)-4-hydroxypiperidine-1-carboxylate収率 59.6%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a suspension of magnesium (1.2 g) and 1,2-dibromoethane (0.11 mL) in diethyl ether (30 mL) was added a solution of 3,4-difluorobenzyl bromide (10 g) in diethyl ether (10 mL) at room temperature under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was diluted with THF (30 mL), and cooled to −78° C. A solution of tert-butyl 4-oxopiperidine-1-carboxylate (5.0 g) in THF (10 mL) was added thereto, and the mixture was allowed to warm to room temperature, and was stirred overnight. To the reaction mixture was added a small amount of 1N hydrochloric acid at 0° C. to quench the reaction. Saturated aqueous potassium sodium tartrate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and recrystallized from ethyl acetate/hexane to give the title compound (4.9 g).

後処理

  1. temperatureto warm to room temperature
  2. stirringwas stirred overnight
  3. customto quench
  4. customthe reaction
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)
  10. customrecrystallized from ethyl acetate/hexane

出典と根拠

ORDレコード
ord-e074c47e000f48caa0e5d4e809cd803a
出典データセット
uspto-grants-2014_10
特許番号
US08865717B2

反応ノート

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