Hydrochloric Acid → 3-(4-Bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoic acid

HRID 238801Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 238801
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[C:30]([C:35]([F:38])([F:37])[F:36])[CH:29]=2)([C:14]2[CH:19]=[C:18]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:17]=[C:16]([F:27])[CH:15]=2)[C:10]([O:12]C)=[O:11])=[CH:4][CH:3]=1.C1COCC1.[Li+].[OH-].Cl>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[C:30]([C:35]([F:38])([F:37])[F:36])[CH:29]=2)([C:14]2[CH:19]=[C:18]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:17]=[C:16]([F:27])[CH:15]=2)[C:10]([OH:12])=[O:11])=[CH:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86613055Methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate

Produkt 1

HCID 594587593-(4-Bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoic acidAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate (865 mg, 1.34 mmol) in MeOH (10 mL)/THF (20 mL) and LiOH (2 N, 10 mL) was stirred at rt overnight. The reaction mixture was made acidic by addition of 1 N HCl to pH=1˜2 and concentrated. The resulting residue was partitioned between EtOAc and sat. NaCl. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by ISCO (40 g siligel column, 0-10% MeOH/DCM over 30 min) to yield 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoic acid as a colorless oil (650 mg, 81% yield). LCMS: RT=2.17 min [M+H] 600.88 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.45 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm).

Aufarbeitung

  1. concentrationconcentrated
  2. customThe resulting residue was partitioned between EtOAc and sat. NaCl
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by ISCO (40 g siligel column, 0-10% MeOH/DCM over 30 min)

Quellen und Nachweise

ORD-Eintrag
ord-dc564014808b4aeabe320ed77294ce10
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642576B2

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