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

HRID 539690

반응식

HRID 539690 반응식
[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

참가 물질

9

반응물 6

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

생성물 1

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

시약·촉매·용매 2

HCID 3283Diethyl Ether용매2회HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-313a2d8d585047c8b67d6c06f4797822
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871766B2

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