Cesium carbonate → chloromethyl (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoate
Reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([O-])([O-])=O.[Cs+].[Cs+].[Cl:22][CH2:23]I.[Sn]>CCO.CN(C=O)C.O.C1(C)C=CC=CC=1>[C:4]([O:3][C:1]([NH:8][C@@H:9]([CH:10]([CH3:11])[CH3:12])[C:13]([O:15][CH2:23][Cl:22])=[O:14])=[O:2])([CH3:5])([CH3:7])[CH3:6]Participants
9
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Procedure
To a solution of N-Boc-valine (10 g, 46.08 mmol) in EtOH (70 mL) was added Cs2CO3 (14.97 g, 46.06 mmol) in a solution of H2O (30 mL). The mixture was stirred at RT for 30 mins, co-evaporated with toluene to dryness, re-dissolved in DMF (100 mL) and cooled in an ice bath. Chloroiodomethane (81.1 g, 460.8 mmol) was added dropwise at 0° C. The mixture was stirred at RT in the dark (tin foil) for 12 h. The mixture was treated with H2O (200 mL), extracted with EtOAc (3×100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel eluted with PE:EA=100:1 to 60:1 to give (S)-chloromethyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate (37%).
Workup
- temperaturecooled in an ice bath
- extractionextracted with EtOAc (3×100 mL)
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by column chromatography on silica gel
- washeluted with PE
Sources & evidence
- ORD record
- ord-db18ec164e3a4b86941d0fbb4f77972c
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328119B2
Reaction notes
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