Boron trifluoride → Tert-butyl 4-(3-chloro-2-hydroxypropyl)-3-oxopiperazine-1-carboxylate
Reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([Li])CCC.B(F)(F)F.[CH2:24]([CH:26]1[O:28][CH2:27]1)[Cl:25]>C1COCC1>[Cl:25][CH2:24][CH:26]([OH:28])[CH2:27][N:11]1[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][C:10]1=[O:14]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
In a 50 0 ml round bottom flask with magnetic stirrer 4-Boc-piperazinone (5.08 g, 25.4 mmol) was dissolved in THF (100 mL) and cooled to −78° C. Butyllithium (1.6M in hexanes) (15.9 mL, 25.4 mmol) was added then and the mixture agitated for 30 minutes at −78° C. Boron trifluoride ethereate (3.19 mL, 25.4 mmol) was added slowly and then epichlorohydrin (1.99 mL, 25.4 mmol). The mixture was agitated for 1 hour at −78° C. and then allowed to warm up and agitated overnight. Reaction was quenched with saturated ammonium chloride, extracted three times with ethyl acetate, extracts washed with brine and evaporated. Purified by column chromatography on silica gel, eluting with 3% MeOH/CH2Cl2 to give the title compound (3.34 g, 45% yield).
Workup
- stirringThe mixture was agitated for 1 hour at −78° C.
- temperatureto warm up
- stirringagitated overnight
- customReaction
- customwas quenched with saturated ammonium chloride
- extractionextracted three times with ethyl acetate
- washextracts washed with brine
- customevaporated
- customPurified by column chromatography on silica gel
- washeluting with 3% MeOH/CH2Cl2
Sources & evidence
- ORD record
- ord-5b800c9de64a41cb936df30949050675
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08883828B2
Reaction notes
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