Methanol → 4-(Boc-amino)-1-cyclopropyl-piperidine
Reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CO.C(O[C:20]1(O[Si](C)(C)C)[CH2:22][CH2:21]1)C.[BH3-]C#N.[Na+]>C1COCC1>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH:20]2[CH2:22][CH2:21]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]Participants
Conditions
- Temperature
- 60 °C
Procedure
To a solution of 14.0 g (0.0699 mol) piperidin-4-yl-carbamic acid tert-butyl ester in 500 mL abs. MeOH 250 g of dried molecular sieves 3 Å were added. Under argon 39.9 mL (0.699 mol) acetic acid and 52.5 mL (0.262 mol) (1-ethoxy-cyclopropoxy)-trimethyl-silane were added. Finally 314.5 mL (0.3145 mol) of a 1 M NaCNBH3-solution in THF were added dropwise. After 20 min at room temperature the reaction mixture was stirred for 6 h at 60° C. The mixture was filtered over “Celite”. The filtrate was concentrated under reduced pressure. The resulting residue was taken up in 700 mL ethyl acetate and washed with 250 mL of a 1 M NaOH-solution. The aqueous layer was extracted with 300 mL ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4 and concentrated under vacuo to give crude (1-cyclopropyl-piperidin-4-yl)-carbamic acid tert-butyl ester as a colorless solid.
Workup
- filtrationThe mixture was filtered over “Celite”
- concentrationThe filtrate was concentrated under reduced pressure
- washwashed with 250 mL of a 1 M NaOH-solution
- extractionThe aqueous layer was extracted with 300 mL ethyl acetate
- washThe combined organic layers were washed with brine
- dry with materialdried over anhydrous MgSO4
- concentrationconcentrated under vacuo
Sources & evidence
- ORD record
- ord-506f6980c55546ac9c986f2c400517dc
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07741341B2
Reaction notes
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