Diethanolamine → tert-butyl (4S)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylate

HRID 80745

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HRID 80745 반응식
[CH3:1][C:2]1([CH3:16])[C:7](=[O:8])[CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1.B(Cl)([C@H]1[C@H](C)C2C(C)(C)C(CC2)C1)[C@H]1[C@H](C)C2C(C)(C)C(CC2)C1.N(CCO)CCO>C1COCC1.CCOCC>[OH:8][C@H:7]1[CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3][C:2]1([CH3:16])[CH3:1]

참가 물질

6

반응물 3

HCID 8113DiethanolamineHCID 16212015(-)DIP-ChlorideHCID 22278899tert-Butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate

생성물 1

HCID 71244736tert-butyl (4S)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylate

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
5 °C

실험 절차

To a solution of tert-butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate (10.0 g, 44.0 mmol) in THF (45 mL) at 0° C. was added dropwise (−)-DIP-Chloride (50-65 wt. % in heptane, 48.9 mL, 79.0 mmol), and the reaction mixture was stirred at 5° C. for 4 days. The reaction mixture was then diluted with Et2O (250 mL) and diethanol amine (8.0 g) was added to give a massive amount of white precipitate. The resulting mixture was vigorously stirred at room temperature for 3 h. The heterogeneous mixture was then filtered through a Buchner funnel packed with Celite®, and the resulting filtrate was concentrated to give a yellow residue. The residue was purified by silica gel chromatography (25-70% EtOAc/heptane) to provide (S)-tert-butyl 4-hydroxy-3,3-dimethylpiperidine-1-carboxylate. (90% ee). Enantiomeric excess determined by Mosher ester analysis. 1H NMR (400 MHz, CDCl3) δ ppm 3.79-3.94 (m, 1 H), 3.53 (d, J=13.4 Hz, 1 H), 3.42 (dd, J=9.2, 4.2 Hz, 1 H), 3.05 (ddd, J=13.2, 9.8, 3.5 Hz, 1 H), 2.74 (d, J=13.1 Hz, 1 H), 1.69-1.80 (m, 2 H), 1.58 (m, 1 H), 1.46 (s, 9 H), 0.97 (s, 3 H), 0.90 (s, 3 H).

후처리

  1. additionwas added
  2. customto give a massive amount of white precipitate
  3. stirringThe resulting mixture was vigorously stirred at room temperature for 3 h
  4. filtrationThe heterogeneous mixture was then filtered through a Buchner funnel
  5. concentrationthe resulting filtrate was concentrated
  6. customto give a yellow residue
  7. customThe residue was purified by silica gel chromatography (25-70% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-dae4d399400348c997be681f2abe7f71
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846656B2

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