Boron tribromide → Anacetrapib metabolite M1

HRID 589579노트

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HRID 589579 반응식
[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

참가 물질

4

반응물 2

HCID 25134Boron tribromideHCID 498494512-Oxazolidinone, 5-[3,5-bis(trifluoromethyl)phenyl]-3-[[4'-fluoro-2'-methoxy-5'-(1-methylethyl)-4-(trifluoromethyl)[1,1'-biphenyl]-2-yl]methyl]-4-methyl-, (4S,5R)-

생성물 1

HCID 11527411Anacetrapib metabolite M1수율 73.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-ad08eb0743b144e1bcbf4d0f406eab88
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233938B2

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