Boron tribromide → Anacetrapib metabolite M1

HRID 589579Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 589579
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[C:33]([F:39])=[CH:32][C:31]=3[O:40]C)[CH:14]2[CH3:42])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.B(Br)(Br)Br>C(Cl)Cl>[F:44][C:2]([F:1])([F:43])[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]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[C:33]([F:39])=[CH:32][C:31]=3[OH:40])[C@H:14]2[CH3:42])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Komponenten

4

Edukt 2

HCID 25134Boron tribromideHCID 49849451HCID 49849451, Verbindung

Produkt 1

HCID 11527411Anacetrapib metabolite M1Ausbeute 73,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl)methyl)-4-methyl-1,3-oxazolidin-2-one (54) [prepared by methods described in WO2007/005572] (1.4 g) in DCM (5 mL) was treated with BBr3 (0.9 mL) at 15-16° C. and the reaction mixture stirred for 1 hr. The mixture was quenched with ice and diluted with EtOAc (150 mL) The mixture was washed with water, sat'd NaHCO3 solution, and brine, dried (Na2SO4), filtered and the solvent concentrated under reduced pressure. The crude product was purified by chromatography on silica gel to give 1.01 g (60%) of 55. 1H NMR (CDCl3) δ: 7.85 (s, 1H), 7.75-7.62 (m, 4H), 7.42 (m, 1H), 6.96 (dd, 1H), 7.69 (dd, 1H), 5.64 (d, 0.5H), 5.39 (d, 0.5H), 4.92-4.80 (m, 1H), 4.18 (d, 0.5H), 3.99 (d, 0.5H), 3.85 (m, 0.5H), 3.75 (m, 0.5H), 3.19 (m, 1H), 1.17-1.25 (m, 6H), 0.57 (d, 1.5H), 0.45 (d, 1.5H).

Aufarbeitung

  1. customThe mixture was quenched with ice
  2. additiondiluted with EtOAc (150 mL) The mixture
  3. washwas washed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationthe solvent concentrated under reduced pressure
  7. customThe crude product was purified by chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-ad08eb0743b144e1bcbf4d0f406eab88
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09233938B2

Notizen zur Reaktion

Wird geladen…