Azetidine → tert-Butyl [(2S)-1-(azetidin-1-yl)-3-methyl-1-oxobutan-2-yl]carbamate
Reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NC[CH2:22][CH2:23][N:24]([CH3:26])C.Cl.ON1C(=O)CCC1=O.CCN(C(C)C)C(C)C.N1CCC1>C(Cl)Cl>[N:24]1([C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:13]([CH3:15])[CH3:14])[CH2:23][CH2:22][CH2:26]1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
(S)-2-(Tert-butoxycarbonylamino)-3-methylbutanoic acid (50.0 g, 230.1 mmol), EDC hydrochloride (52.9 g, 276.2 mmol) and 1-hydroxypyrrolidine-2,5-dione (39.7 g, 345.2 mmol) was mixed in DCM (180 mL). The mixture was cooled to 0° C. and DIPEA (160 mL, 920.6 mmol) was added. After 1 h at 0° C. was azetidine (18.62 mL, 276.2 mmol) added. The resultant mixture was stirred at rt over night. The mixture was concentrated and the residue dissolved in DCM (200 mL). The organic phase was washed with NaHCO3 (saturated, 2×150 mL), HCl (1M aq. solution, 2×200 mL) and brine (150 mL), filtered through a phase separator and concentrated under reduced pressure to give the title compound (42 g, 71%). The obtained crude product was used without further purification.
Workup
- concentrationThe mixture was concentrated
- dissolutionthe residue dissolved in DCM (200 mL)
- washThe organic phase was washed with NaHCO3 (saturated, 2×150 mL), HCl (1M aq. solution, 2×200 mL) and brine (150 mL)
- filtrationfiltered through a phase separator
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-47e54f0389574643b9bd888d46e5d6e3
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08361998B2
Reaction notes
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