Pyridine → Pyridinium chloride

HRID 882365Notes

Reaction equation

HRID 882365 reaction equation
[Cl:1][C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[CH3:8][C:9]1([CH3:16])[O:13][CH:12](NC)[CH2:11][O:10]1.[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[CH3:16][C:9]1([CH3:8])[O:13][CH:12]([CH2:18][NH:17][C:2](=[O:3])[O:4][CH:5]([Cl:7])[CH3:6])[CH2:11][O:10]1.[ClH:1].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 5213051-Chloroethyl chloroformateHCID 21108541HCID 21108541, compound

Product 2

HCID 10176127Pyridinium chlorideHCID 86696301HCID 86696301, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate (1.46 g, 1.1 mL, 10.2 mmol) was reacted with (2,2-dimethyl-[1,3]-dioxolan-4-yl)-methylamine (Aldrich, 1.21 g, 1.2 mL, 8.98 mmol) and pyridine (870 mg, 0.89 mL, 11.0 mmol) in methylene chloride (15 mL) at 78° C. for 3 h to give 1-chloroethyl (2,2-dimethyl-1,3-dioxolan-4-yl)methylcarbamate with pyridine hydrochloride (1:1). A portion of this material (622 mg, 1.76 mmol) in dimethylformamide (5 mL) 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 (201 mg, 0.326 mmol) in the presence of cesium carbonate (806.9 mg, 2.48 mmol) in dimethylformamide (7 mL) overnight to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethylcarbamoyloxy)-ethyl ester as a white solid (97.7 mg, 36% yield). MS (ES+) m/z calcd. for C40H45C12F2N4O8: [(M+H)+]: 817, found: 817

Sources & evidence

ORD record
ord-c69b176c6b7f40a695b7e7179793401b
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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