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Hydrochloric Acid → rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid

HRID 1806897
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1806897
C[O:2][C:3]([CH:5]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=2[F:17])[C:8]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[F:27])([C:18]#[N:19])[CH:7]([CH2:28][C:29]([CH:32]2[CH2:34][CH2:33]2)([CH3:31])[CH3:30])[NH:6]1)=[O:4].[OH-].[Na+].CO.Cl>O1CCCC1>[Cl:16][C:12]1[C:11]([F:17])=[C:10]([CH:9]2[C:8]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[CH:7]([CH2:28][C:29]([CH:32]3[CH2:33][CH2:34]3)([CH3:31])[CH3:30])[NH:6][CH:5]2[C:3]([OH:4])=[O:2])[CH:15]=[CH:14][CH:13]=1
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Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 67297219rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid methyl ester

Produkt 1

HCID 67296911
rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid
Ausbeute 84,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid methyl ester prepared in Example 99b (0.95 g, 1.87 mmol) in tetrahydrofuran (40 mL) was added an aqueous solution (20 mL) of NaOH (0.15 g, 3.7 mmol) and methanol (20 mL). The reaction mixture was stirred at room temperature for 18 h. The “pH” of the mixture was adjusted to 5 by aqueous HCl solution. The mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over MgSO4, concentrated, and trituated with dichloromethane and hexanes to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid as a white solid (0.78 g, 80%)

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. customThe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-cc320c2f6b3b43d8b7c7acf5f297c4bb
Quelldatensatz
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08354444B2

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