Lithium Hydroxide → rac-4-({[(2S,3S,4S)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,3-dichloro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-benzoic acid

HRID 909047Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 909047
C[O:2][C:3](=[O:42])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([N:14]2[CH2:18][C@@H:17]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C@@:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])([C:24]#[N:25])[C@H:15]2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=2[Cl:41])=[O:13])=[CH:6][CH:5]=1.[Li+].[OH-]>C1COCC1.CO>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C@@:16]2([C:24]#[N:25])[C@H:17]([CH2:19][C:20]([CH3:23])([CH3:21])[CH3:22])[CH2:18][N:14]([C:12]([NH:11][CH2:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:42])=[O:2])=[CH:5][CH:6]=3)=[O:13])[C@@H:15]2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[C:35]=2[Cl:41])=[C:27]([F:33])[CH:28]=1

Komponenten

4

Edukt 2

HCID 3939Lithium HydroxideHCID 67095189rac-4-({[(2S,3S,4S)-2-(2,3-dichloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-benzoic acid methyl ester

Produkt 1

HCID 67095479rac-4-({[(2S,3S,4S)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,3-dichloro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-benzoic acidAusbeute 99,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21899815MeOH tetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of rac-4-({[(2S,3S,4S)-2-(2,3-dichloro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-benzoic acid methyl ester (44.2 mg, 0.07 mmol) in THF/MeOH (0.6 mL/0.2 mL) was added 4 N LiOH (0.2 mL), and the reaction mixture was stirred at rt overnight. The reaction mixture was concentrated and quenched with 2 NH2SO4, extracted with EtOAc, and washed with water, brine. The organic phase was separated, and dried over Na2SO4. The mixture was then concentrated to give rac-4-({[(2S,3S,4S)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,3-dichloro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-methyl)-benzoic acid (43.0 mg, 99.6%). LC-MS (ES+/−) m/z Calcd for C31H29Cl3FN3O3: 617; Found: 617.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. customquenched with 2 NH2SO4
  3. extractionextracted with EtOAc
  4. washwashed with water, brine
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. concentrationThe mixture was then concentrated

Quellen und Nachweise

ORD-Eintrag
ord-b0f9ff8adf5b47c19c74badad454d382
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017607B2

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