Pyridine → 1-Chloroethyl 1-methylethyl carbonate
Reaction equation
Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[CH3:8][CH:9]([OH:11])[CH3:10].N1C=CC=CC=1>C(Cl)Cl>[C:2](=[O:3])([O:11][CH:9]([CH3:10])[CH3:8])[O:4][CH:5]([Cl:7])[CH3:6]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate (Oakwood Products, 1.99 g, 1.5 mL, 13.9 mmol) was reacted with 2-propanol (785 mg, 1 mL, 13.0 mmol) and pyridine (1.27 g, 1.3 mL, 16.1 mmol) in methylene chloride (11 mL) at room temperature for 4 h to give 1-chloroethyl isopropyl carbonate. A portion of 1-chloroethyl isopropyl carbonate (221.6 mg, 1.33 mmol) was then reacted with chiral 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (150.3 mg, 244 μmol) in the presence of cesium carbonate (478 mg, 1.47 mmol) in dimethylformamide (5 mL) overnight to give, after flash chromatography purification (hexane/ethyl acetate, 80/20 to 20/80), 1-(isopropoxycarbonyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (134.4 mg, 73% yield). MS (ES+) m/z calcd. for C37H40Cl2F2N3O7: [(M+H)+]: 746, found: 746
Sources & evidence
- ORD record
- ord-8132e36bdd6d4a0b899211230a4c7480
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08993614B2
Reaction notes
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