Potassium Carbonate → methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 604656Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 604656
[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[C:25](Br)=[CH:24][CH:23]=[C:22]([Cl:27])[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[C:41](B3OC(C)(C)C(C)(C)O3)[C:40]=2[CH3:58])=[CH:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(O)C>[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[C:25]([C:34]4[CH:35]=[C:36]([C:39]5[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=5[CH3:58])[CH:37]=[CH:38][C:33]=4[O:32][CH3:31])=[CH:24][CH:23]=[C:22]([Cl:27])[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one2×HCID 67057751Methyl 4'-methoxy-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate

Produkt 1

HCID 57576282methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylateAusbeute 22,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 702EthanolLösungsmittel

Versuchsvorschrift

(4S,5R)-5-[3,5-bis(3-trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 9) (500 mg, 0.966 mmol), methyl 4′-methoxy-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (554 mg, 1.45 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (158 mg, 20%), aqueous potassium carbonate (966 μL, 2M, 1.93 mmol) and ethanol (5 mL) were heated in an 80° C. oil bath for 1 h. Volatiles were then removed from the crude mixture under reduced pressure. The pot residue was treated with water followed by EtOAc extraction. The combined extracts were dried over Na2SO4 followed by filtration and concentration to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, 0-40% EtOAc in hexanes) to afford methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (152 mg), as a yellow glass. LCMS calc.=692.15; found=693.19 (M+1).

Aufarbeitung

  1. customVolatiles were then removed from the crude mixture under reduced pressure
  2. additionThe pot residue was treated with water
  3. extractionfollowed by EtOAc extraction
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfollowed by filtration and concentration
  6. customto afford a dark oil
  7. customThe resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, 0-40% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-bd281eea119b46a9b879ba52f94ca234
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07910592B2

Notizen zur Reaktion

Wird geladen…