HuagongsheHuagongshe Chemistry Print Report · For research reference only
Lithium hydroxide, monohydrate → 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}-methyl)-2-fluoro-benzoic acid
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | Lithium hydroxide, monohydrate | HCID 168937 | — |
| Reactant | Rac-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}-methyl)-2-fluoro-benzoic acid methyl ester | HCID 53357095 | — |
| Solvent | Water | HCID 962 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Product | 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}-methyl)-2-fluoro-benzoic acid | HCID 53357094 | 97.4% |
Reaction Steps
In a manner similar to the method described in Example 380, rac-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}-methyl)-2-fluoro-benzoic acid methyl ester (80.3 mg, 0.127 mmol) in THF (9 ml) was reacted with lithium hydroxide hydrate (37.6 mg, 0.896 mmol) in water (4.5 mL) to give rac-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}-methyl)-2-fluoro-benzoic acid as a white lyophilized solid (76.5 mg, 97%). HRMS (ES+) m/z Calcd C31H28Cl2F3N3O3+H [(M+H): 618.1533. Found: 618.1533.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US08354444B2 |
| Source dataset | uspto-grants-2013_01 |
| ORD ID | ord-dc02a547e67348b29173efc92ebac50a |
| Source note | uspto-grants-2013_01 |