Hydrogen chloride-ethyl acetate → N-[(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]isoxazol-3-yl}oxy)-1-methylethyl]acetamide
Reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[O:18][N:17]=[C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=O)[O:25]C(C)(C)C)[CH3:22])[CH:15]=4)=[N:11][C:10]=3[CH:31]=2)[CH2:3][CH2:2]1.Cl.[C:33](OCC)(=O)C>C(OCC)(=O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[O:18][N:17]=[C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:25])[CH3:33])[CH3:22])[CH:15]=4)=[N:11][C:10]=3[CH:31]=2)[CH2:2][CH2:3]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of tert-butyl [(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]isoxazol-3-yl}oxy)-1-methylethyl]carbamate (510 mg) in ethyl acetate (11 mL) was added 4M hydrogen chloride/ethyl acetate (12 mL), and the mixture was stirred at room temperature for 5 hr. The solvent was evaporated under reduced pressure, and the residue was dissolved in pyridine (1.5 ml). Acetic anhydride (1.5 mL) was added thereto, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate/methanol), and recrystallized (hexane/ethyl acetate) to give the title compound (182 mg).
Workup
- customThe solvent was evaporated under reduced pressure
- dissolutionthe residue was dissolved in pyridine (1.5 ml)
- additionAcetic anhydride (1.5 mL) was added
- stirringthe mixture was stirred at room temperature overnight
- concentrationThe reaction mixture was concentrated under reduced pressure
- customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate/methanol)
- customrecrystallized (hexane/ethyl acetate)
Sources & evidence
- ORD record
- ord-cbf3678df68f4839b410786b24985a44
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08729102B2
Reaction notes
Loading…