HCID 11664349, compound → HCID 11621422, compound

HRID 1028591Notes

Reaction equation

HRID 1028591 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([C:9]2[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:10]=2[CH2:11][N:12]2[C@@H:16]([CH3:17])[C@@H:15]([C:18]3[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=3)[O:14][C:13]2=[O:32])[S:7][CH:8]=1)(=[O:3])[CH3:2].[CH3:41][Mg+].[Br-]>CCOCC>[F:31][C:28]([F:29])([F:30])[C:20]1[CH:19]=[C:18]([C@H:15]2[O:14][C:13](=[O:32])[N:12]([CH2:11][C:10]3[CH:33]=[C:34]([C:37]([F:40])([F:39])[F:38])[CH:35]=[CH:36][C:9]=3[C:6]3[S:7][CH:8]=[C:4]([C:1]([OH:3])([CH3:41])[CH3:2])[N:5]=3)[C@H:16]2[CH3:17])[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=1

Participants

4

Reactant 2

HCID 11664349HCID 11664349, compoundHCID 178418689HCID 178418689, compound2×

Product 1

HCID 11621422HCID 11621422, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a −40° C. solution of (4S,5R)-3-[2-(4-acetyl-1,3-thiazol-2-yl)-5-(trifluoromethyl)benzyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (Example 135) (38.1 mg, 0.064 mmol) in THF/heptanes (1:1, 8 mL) was added MeMgBr (21 μL of a 3M solution in Et2O, 0.07 mmol). The temperature was maintained between −40° C. and −20° C. and the reaction was monitored closely by TLC; additional MeMgBr was added dropwise until nearly all starting ketone was consumed. At this point, the reaction was quenched by pouring it into saturated NH4Cl (15 mL). The mixture was extracted with EtOAc (50 mL) and the organic layer was washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (10 to 60% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[4-(1-hydroxy-1-methylethyl)-1,3-thiazol-2-yl]-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.20 (40% EtOAc/hexanes). LCMS=613 (M+1)+. 1H NMR (CD2Cl2, 500 MHz) δ 7.90 (s, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.77 (s, 3H), 7.71 (d, J=8.3 Hz, 1H), 7.32 (s, 1H), 5.59 (d, J=8.0 Hz, 1H), 5.28 (d, J=15.8 Hz, 1H), 4.74 (d, J=15.8 Hz, 1H), 3.89 (m, 1H), 3.01 (bs, 1H), 1.63 (s, 3H), 1.62 (s, 3H), 0.64 (d, J=6.5 Hz, 3H).

Workup

  1. temperatureThe temperature was maintained between −40° C. and −20° C.
  2. customwas consumed
  3. customAt this point, the reaction was quenched
  4. additionby pouring it into saturated NH4Cl (15 mL)
  5. extractionThe mixture was extracted with EtOAc (50 mL)
  6. washthe organic layer was washed with water and brine (15 mL each)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the residue by flash chromatography on silica gel (10 to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9bc08ce2308f4e3387601d16aafc3d4d
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

Loading…