Water → Tert-butyl 4-cyclobutylpiperazine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[C:15]1(=O)[CH2:18][CH2:17][CH2:16]1.C([BH3-])#N.[Na+]>C1COCC1.C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:15]2[CH2:18][CH2:17][CH2:16]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
7
Conditions
- Temperature
- 60 °C
Procedure
To a solution of 1-tert-butyloxycarbonylpiperazine (2.24 g, 12.0 mmol) in THF (20 ml) were added water (0.2 ml), cyclobutanone (1.35 ml, 18.1 mmol), acetic acid (2.20 ml) and sodium cyanoborohydride (18 ml of a 1M solution in THF, 18 mmol). The mixture was stirred at 60° C. over night, concentrated, and the residue was mixed with water (50 ml) and 1N aqueous hydrochloric acid (15 ml). The solution was washed with ethyl acetate (2×30 ml), made basic by addition of potassium carbonate, extracted (2×20 ml ethyl acetate), and the combined extracts were washed with brine, dried with magnesium sulphate, and concentrated. 1.1 g (38%) of the title compound was obtained as a colourless oil.
Workup
- concentrationconcentrated
- additionthe residue was mixed with water (50 ml) and 1N aqueous hydrochloric acid (15 ml)
- washThe solution was washed with ethyl acetate (2×30 ml)
- additionmade basic by addition of potassium carbonate
- extractionextracted (2×20 ml ethyl acetate)
- washthe combined extracts were washed with brine
- dry with materialdried with magnesium sulphate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-22f4c626132d4edcb60da81d7602ce90
- Source dataset
- uspto-grants-2007_04
- Patent number
- US07208497B2
Reaction notes
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