Diethyl Ether → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 384701노트

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HRID 384701 반응식
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1([C:21](OCC)=[O:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.CCOCC>C1COCC1.C(Cl)(Cl)Cl>[F:7][C:8]1([CH2:21][OH:22])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]1

참가 물질

6

반응물 3

HCID 3283Diethyl EtherHCID 21226445Aluminium lithium hydrideHCID 21306965Ethyl N-Boc-4-fluoropiperidine-4-carboxylate

생성물 1

HCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate수율 69%

시약·촉매·용매 2

HCID 6212Chloroform용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

Lithium aluminium hydride (1M in THF) (2.36 mL, 2.361 mmol) was added dropwise to a stirred solution of 1-tert-butyl 4-ethyl 4-fluoropiperidine-1,4-dicarboxylate (325 mg, 1.180 mmol) in THF (5.90 mL) cooled to 0° C. After 10 min ether (15 mL) was added and the reaction was quenched by sequential dropwise addition of water (0.1 mL), 10% NaOH (0.1 mL) and water (0.3 mL). The mixture was stirred at room temperature and the lithium salts that had precipitated were filtered off and washed with fresh ether. The organic filtrates were combined and solvent was removed in vacuo to leave a clear gum. The crude product was taken up in chloroform and loaded onto a 25+M Biotage silica column. Chromatography, eluting with a gradient of EtOAc in hexanes, gave tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (189 mg, 0.810 mmol, 69%) as a clear gum.

후처리

  1. customthe reaction was quenched by sequential dropwise addition of water (0.1 mL), 10% NaOH (0.1 mL) and water (0.3 mL)
  2. customthe lithium salts that had precipitated
  3. filtrationwere filtered off
  4. washwashed with fresh ether
  5. customsolvent was removed in vacuo
  6. customto leave a clear gum
  7. washChromatography, eluting with a gradient of EtOAc in hexanes

출처 및 근거

ORD 기록
ord-6e1add202b5145a99aee42489b98cbe3
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367658B2

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