Hydrochloric Acid → 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoic acid

HRID 1807315

Reaktionsgleichung

Reaktionsgleichung von HRID 1807315
[Cl:1][C:2]1[C:3]([F:45])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37]C)=[O:36])=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.C1COCC1.[OH-].[Na+].Cl>CO>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C@@:12]2([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:25])[CH3:27])[NH:10][C@@H:9]([C:28]([NH:30][C:31]3[CH:40]=[CH:39][C:34]([C:35]([OH:37])=[O:36])=[C:33]([C:41]([F:43])([F:44])[F:42])[CH:32]=3)=[O:29])[C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:45])=[C:16]([F:22])[CH:17]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59249260methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoate

Produkt 1

HCID 533577404-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoic acidAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

In a 50 mL round-bottomed flask, methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoate (290 mg, 434 μmol, Eq: 1.00) was combined with THF (8 ml) and MeOH (8.00 ml) to give a colorless solution. 1.5 M NaOH (3 ml, 4.5 mmol, Eq: 10.4) was added. The reaction mixture was heated to 50° C. and stirred for 3 h. The reaction mixture was acidified with 1N HCl and was extracted with EtOAc (3×15 mL). The organic layers were combined, washed with saturated NaCl (1×10 mL), dried over Na2SO4 and concentrated in vacuum. The crude material was dissolved in DMSO and purified by preparative HPLC (70-100% ACETONITRILE/water). Obtained was a white solid (130 mg, 46% yield). MS (ES+) m/z Calcd: [(M+H)+]: 654. found: 654.

Aufarbeitung

  1. customto give a colorless solution
  2. extractionwas extracted with EtOAc (3×15 mL)
  3. washwashed with saturated NaCl (1×10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuum
  6. dissolutionThe crude material was dissolved in DMSO
  7. custompurified by preparative HPLC (70-100% ACETONITRILE/water)
  8. customObtained

Quellen und Nachweise

ORD-Eintrag
ord-edac1b0386cd480e9e80523012251acb
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354444B2

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