Pyridine → 1-Chloroethyl Cyclohexyl Carbonate
Reaction equation
Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[CH:8]1([OH:14])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.N1C=CC=CC=1>C(Cl)Cl>[C:2](=[O:3])([O:14][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[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 cyclohexanol (Alfa Aesar, 1.33 g, 1.4 mL, 13.3 mmol) and pyridine (1.27 g, 1.3 mL, 16.1 mmol) in methylene chloride (11 mL) at −78° C. for 3 h to give 1-chloroethyl cyclohexyl carbonate. A portion of 1-chloroethyl cyclohexyl carbonate (253 mg, 1.22 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, 0.244 mmol) in the presence of cesium carbonate (487.4 mg, 1.5 mmol) in dimethylformamide (5 mL) overnight to give, after flash chromatography purification (hexane/ethyl acetate, 80/20 to 20/80), 1-(cyclohexyloxycarbonyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (135.4 mg, 70% yield). MS (ES+) m/z calcd. for C40H44Cl2F2N3O7: [(M+H)+]: 786, found: 786
Sources & evidence
- ORD record
- ord-a11875386b57479ea8a272c98a457542
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08993614B2
Reaction notes
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