Hydrochloric Acid → Benzyl 4[-2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate
Reaction equation
[OH:1][CH2:2][CH2:3][C@H:4]1[CH2:6][C@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])(C)C)=[O:14])[CH2:9][CH2:8]1.Cl.C(OC(Cl)=O)[C:22]1[CH:27]=[CH:26]C=[CH:24][CH:23]=1>O1CCOCC1>[OH:1][CH2:2][CH2:3][CH:4]1[CH2:6][CH:5]1[CH:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][CH2:16][C:19]2[CH:26]=[CH:27][CH:22]=[CH:23][CH:24]=2)=[O:14])[CH2:11][CH2:12]1Participants
Procedure
Cis tert-butyl 4-[2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate (2.0 g, 7.44 mmol) was treated with 4M HCl in dioxane (200 mL) at room temperature for 2 hours. The mixture was concentrated under reduced pressure and the residue taken up in 200 mL DCM. To this solution was added TEA (10.0 mL, 7.64 mmol) followed by benzylchloroformate (1.30 g, 7.64 mmol) and the resulting mixture stirred at room temperature overnight. The mixture was washed with 1N aqueous HCl (75 mL), followed by saturated aqueous sodium bicarbonate (75 mL) and brine (75 mL). The organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via Biotage (40M+ silica gel) eluting with a gradient of 0-80% ethyl acetate to afford the title compound as a viscous oil.
Workup
- concentrationThe mixture was concentrated under reduced pressure
- washThe mixture was washed with 1N aqueous HCl (75 mL)
- dry with materialThe organics were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified via Biotage (40M+ silica gel)
- washeluting with a gradient of 0-80% ethyl acetate
Sources & evidence
- ORD record
- ord-1be6f356d24f485db7788136a60da68f
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08957062B2
Reaction notes
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