Piperidin-4-ol → Ethyl 3-cyano-3-(4-hydroxypiperidin-1-YL)pyrrolidine-1-carboxylate

HRID 1642481노트

반응식

HRID 1642481 반응식
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.O=[C:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10]1.[C-:19]#[N:20].C([Al+]CC)C>ClCCCl.ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:19]([C:9]1([N:5]2[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]2)[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10]1)#[N:20]

참가 물질

7

반응물 3

HCID 79341Piperidin-4-olHCID 277754Ethyl 3-oxopyrrolidine-1-carboxylateHCID 16686413Diethyl aluminum cyanide

생성물 1

HCID 57619828Ethyl 3-cyano-3-(4-hydroxypiperidin-1-YL)pyrrolidine-1-carboxylate수율 97.9%

시약·촉매·용매 3

HCID 11026Titanium isopropoxide촉매HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

실험 절차

To a stirred solution of 4-hydroxypiperidine (464 mg, 4.58 mmol) and ethyl 3-oxopyrrolidine-1-carboxylate (610 mg, 3.82 mmol) in 1,2-dichloroethane (25 mL) was added titanium isopropoxide (1.09 g, 3.82 mmol), and the mixture was stirred at room temperature overnight. Then a 1.0 M solution of diethylaluminum cyanide (1.02 g, 9.17 mmol) was added at room temperature and the mixture was stirred for 24 h. Diluted with dichloromethane (25 mL) and quenched with saturated ammonium chloride solution (10 mL) at 0° C. Then mixture was filtered through a small pad of celite, and the resulting filtrate was concentrated in vacuo to afford the title compound as a yellow gum (1.0 g). 1H NMR (CDCl3, 400 MHz): δ 4.22 (q, 2H), 4.21-4.1 (dd, 1H), 3.79-3.62 (m, 3H), 3.38 (dd, 1H), 2.9 (brs, 1H), 2.7 (brs, 1H), 2.54-2.35 (m, 3H), 2.18-1.85 (brm, 3H), 1.68-1.45 (m, 3H), 1.25 (t, 3H). MS (M+1): 268.14.

후처리

  1. stirringthe mixture was stirred for 24 h
  2. customquenched with saturated ammonium chloride solution (10 mL) at 0° C
  3. filtrationThen mixture was filtered through a small pad of celite
  4. concentrationthe resulting filtrate was concentrated in vacuo

출처 및 근거

ORD 기록
ord-16c846a6c2334cfebe37f2a4b9414591
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08119661B2

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