Benzyl 3-formylpiperidine-1-carboxylate → (R,S)-3-(1-Hydroxyethyl)-piperidine-1-carboxylic acid benzyl ester

HRID 48475

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HRID 48475 반응식
[Zn](C)[CH3:2].[CH2:4]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH:16]([CH:20]=[O:21])[CH2:15]1)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>CCOCC.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[CH2:4]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([C@@H:20]([OH:21])[CH3:2])[CH2:15]1)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

참가 물질

5

반응물 2

HCID 9899653Benzyl 3-formylpiperidine-1-carboxylateHCID 178477796HCID 178477796, 화합물

생성물 1

HCID 60072571(R,S)-3-(1-Hydroxyethyl)-piperidine-1-carboxylic acid benzyl ester수율 51%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 3283Diethyl Ether용매2회

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온도
-78 °C

실험 절차

Using Schlenck glassware and air-free conditions, anhydrous ethyl ether freshly distilled from sodium/benzophenone (2.43 mL) was added to catalyst 13 prepared according to Example 11, protocol 1. Freshly distilled titanium tetraisopropoxide (0.430 mL, 1.46 mmol) was added, and the reaction was cooled to −78° C. Commercial Me2Zn (1.21 mL, 2 M in toluene) was added, and the reaction was stirred at −78° C. for 1 hour. Aldehyde 9 (0.300 g, 1.21 mmol) in Et2O (0.3 mL) was added, and the reaction was warmed to −30° C. and stirred overnight. The reaction was then quenched at −30° C. with saturated aqueous NH4Cl. Et2O was added, and the reaction was filtered through Celite wet with Et2O. The reaction was dried with sodium sulfate, filtered, concentrated, and purified using an ISCO CombiFlash column (silica, 2:1 Hexane:EtOAc) to obtain 15 (0.162 g, 51%). HLPC analysis of the product presented in the Figures. 1H NMR (CDCl3, 300 MHz) 7.43-7.31 (5H, broad s), 5.16 (2H, s), 4.30-3.60 (2H, broad m), 3.63 (1H, dq, J=6.4, 6.4 Hz), 3.30-2.70 (2H, broad s), 2.15-1.90 (1H, broad s), 1.84-1.72 (1H, m), 1.76-1.56, (1H, m), 1.58-1.36 (2H, m), 1.23 (3H, d, J=6.4 Hz) ppm. 13C NMR (CDCl3, 75 MHz) 155.81, 137.04, 128.61, 128.08, 127.93, 68.35, 67.19, 46.61, 45.02, 43.25, 27.08, 24.37, 20.95 ppm. LRMS m/z 263.68 (M+, C15H21NO3, requires 263.15.

후처리

  1. distillationfreshly distilled from sodium/benzophenone (2.43 mL)
  2. additionwas added to catalyst 13
  3. customprepared
  4. temperaturethe reaction was warmed to −30° C.
  5. stirringstirred overnight
  6. customThe reaction was then quenched at −30° C. with saturated aqueous NH4Cl
  7. additionEt2O was added
  8. filtrationthe reaction was filtered through Celite wet with Et2O
  9. dry with materialThe reaction was dried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified

출처 및 근거

ORD 기록
ord-7426ba4a8e5b411b89b4811a780dc53c
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06703508B2

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