Piperidin-4-ol → Ethyl 3-cyano-3-(4-hydroxypiperidin-1-YL)pyrrolidine-1-carboxylate
Reaction equation
[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]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
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.
Workup
- stirringthe mixture was stirred for 24 h
- customquenched with saturated ammonium chloride solution (10 mL) at 0° C
- filtrationThen mixture was filtered through a small pad of celite
- concentrationthe resulting filtrate was concentrated in vacuo
Sources & evidence
- ORD record
- ord-16c846a6c2334cfebe37f2a4b9414591
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119661B2
Reaction notes
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