Reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][O:8][C:7]([C@H:10]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH3:11])=[N:6]1)=[O:4].C1CCN2C(=NCCC2)CC1.BrC(Cl)(Cl)Cl>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([C@H:10]([NH:12][C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH3:11])[O:8][CH:9]=1)=[O:4]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
In a round-bottomed flask, 2-((R)-1-tert-butoxycarbonylamino-ethyl)-4,5-dihydro-oxazole-4-carboxylic acid methyl ester (337 mg, 1.18 mmol) was dissolved in dichloromethane (11 ml). The solution was cooled to −16° C. (NaCl/ice bath) and DBU (0.35 ml, 2.32 mmol) was added. After 5 min, bromotrichloromethane (0.13 ml, 1.33 mmol) was added and the reaction mixture was allowed slowly to warm to room temperature and stirred for 4 days. The reaction was quenched with 0.1 M aqueous HCl and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc) to afford 152 mg (48%) of 2-((R)-1-tert-butoxycarbonylamino-ethyl)-oxazole-4-carboxylic acid methyl ester as an off-white solid.
Workup
- additionwas added
- customThe reaction was quenched with 0.1 M aqueous HCl
- extractionextracted with EtOAc (2×)
- washThe combined organic layers were washed with water and brine
- dry with materialthen dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc)
Sources & evidence
- ORD record
- ord-d1203247537745eb862daa5a76e28614
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658646B2
Linked notes
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