Toluene → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5'-bromo-4-fluoro-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 2093164Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2093164
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Br:31][C:32]1[CH:33]=[CH:34][C:35]([O:41][CH3:42])=[C:36](B(O)O)[CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[F:10][C:9]([F:11])([F:12])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[C:34]3[CH:33]=[C:32]([Br:31])[CH:37]=[CH:36][C:35]=3[O:41][CH3:42])[C@H:14]2[CH3:28])[CH:4]=[C:3]([C:2]([F:29])([F:30])[F:1])[CH:8]=1

Komponenten

8

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 45327305-Bromo-2-methoxyphenylboronic acidHCID 59135189(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one

Produkt 1

HCID 57704830(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5'-bromo-4-fluoro-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one (600 mg, 1.2 mmol), (5-bromo-2-methoxyphenyl)boronic acid (319 mg, 1.38 mmol), sodium carbonate aqueous solution (1.27 mL, 2M, 2.54 mmol), toluene (3.5 mL) and ethanol (400 μL) were mixed and stirred at room temperature for 45 minutes followed by addition of tetrakis(triphenylphosphine)palladium(0) (87 mg, 4.5 mol %). The resulting mixture was heated in a 90° C. oil bath for 24 hours to complete the reaction. The crude reaction was diluted with brine and extracted with ethyl acetate. The combined extracts were dried over Na2SO4 followed by filtration and concentration in vacuo to afford a dark oil. The crude oil was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixtureaffording (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5′-bromo-4-fluoro-2′-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=607.04; found=607.98 (M+1)+.

Aufarbeitung

  1. temperatureThe resulting mixture was heated in a 90° C. oil bath for 24 hours
  2. customthe reaction
  3. customThe crude reaction
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. filtrationfollowed by filtration and concentration in vacuo
  7. customto afford a dark oil
  8. customThe crude oil was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  9. washeluting with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient

Quellen und Nachweise

ORD-Eintrag
ord-eac119b5c18f428181ec5962275ae3f5
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440702B2

Notizen zur Reaktion

Wird geladen…