Boron tribromide → (4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-3-((4'-fluoro-2',3'-dihydroxy-5'-isopropyl-4-(trifluoromethyl)biphenyl-2-yl)methyl)-4-methyl-1,3-oxazolidin-2-one

HRID 1028631Notes

Reaction equation

HRID 1028631 reaction equation
B(Br)(Br)Br.[F:5][C:6]([F:49])([F:48])[C:7]1[CH:8]=[C:9]([C@H:17]2[O:21][C:20](=[O:22])[N:19]([CH2:23][C:24]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=3[C:34]3[CH:39]=[C:38]([CH:40]([CH3:42])[CH3:41])[C:37]([F:43])=[C:36]([OH:44])[C:35]=3[O:45]C)[C@H:18]2[CH3:47])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1>C(Cl)Cl.O>[F:49][C:6]([F:5])([F:48])[C:7]1[CH:8]=[C:9]([C@H:17]2[O:21][C:20](=[O:22])[N:19]([CH2:23][C:24]3[CH:29]=[C:28]([C:30]([F:31])([F:33])[F:32])[CH:27]=[CH:26][C:25]=3[C:34]3[CH:39]=[C:38]([CH:40]([CH3:41])[CH3:42])[C:37]([F:43])=[C:36]([OH:44])[C:35]=3[OH:45])[C@H:18]2[CH3:47])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 11650409(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-3'-hydroxy-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 11549128(4S,5R)-5-(3,5-Bis(trifluoromethyl)phenyl)-3-((4'-fluoro-2',3'-dihydroxy-5'-isopropyl-4-(trifluoromethyl)biphenyl-2-yl)methyl)-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Boron tribromide (17.4 mg, 6.6 μL, 0.0692 mmol) was added to a stirred solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-3′-hydroxy-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (22.6 mg, 0.0346 mmol) in dry CH2Cl2 (1 mL) at −78° C. at room temperature under N2 and the reaction was stirred for 8 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by chiral HPLC (IA column, 20×250 mm, 15% i-PrOH in heptane) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-2′,3′-dihydroxy-5′-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.24 (20% EtOAc in hexanes). LCMS calc.=640.2; found=640.2 (M+1)+. 1H NMR (600 MHz, CDCl3, 1:1 mixture of atropisomers) δ 7.85 (s, 1H), 7.70-7.62 (m, 4H), 7.41 (m, 1H), 6.52 (s, 0.5H), 6.51 (s, 0.5H), 6.20 (br s, 2H), 5.65 (d, J=7.9 Hz, 0.5H), 5.38 (d, J=8.0 Hz, 0.5H), 5.00 (d, J=15.5 Hz, 0.5H), 4.92 (d, J=15.6 Hz, 0.5H), 4.15 (d, J=15.5 Hz, 0.5H), 4.02 (d, J=15.6 Hz, 0.5H), 3.88 (t, J=6.7 Hz, 0.5H), 3.77 (t, J=6.7 Hz, 0.5H), 3.19-3.13 (m, 1H), 1.26-1.17 (m, 6H), 0.59 (d, J=6.1 Hz, 1.5H), 0.48 (d, J=6.2 Hz, 1.5H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by chiral HPLC (IA column, 20×250 mm, 15% i-PrOH in heptane)

Sources & evidence

ORD record
ord-9d2b631418c7445c8ce8d0727241d911
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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