HCID 11512623, compound → HCID 11635729, compound

HRID 1028589Notes

Reaction equation

HRID 1028589 reaction equation
[F:1][C:2]([F:39])([F:38])[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:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[S:31][CH:32]=[C:33]([CH:35]=[O:36])[N:34]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:40][Mg+].[Br-]>CCOCC>[F:39][C:2]([F:1])([F:38])[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[S:31][CH:32]=[C:33]([CH:35]([OH:36])[CH3:40])[N:34]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 2

HCID 11512623HCID 11512623, compoundHCID 178418689HCID 178418689, compound2×

Product 1

HCID 11635729HCID 11635729, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a −40° C. solution of 2-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbaldehyde (Example 133) (43.9 mg, 0.075 mmol) in Et2O (7.5 mL) was added MeMgBr (30 μL of a 3M solution in Et2O, 0.10 mmol). The reaction was monitored closely by TLC and additional MeMgBr was added dropwise until nearly all starting aldehyde 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 (5 to 50% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[4-(1-hydroxyethyl)-1,3-thiazol-2-yl]-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.17 (40% EtOAc/hexanes). LCMS=599.1 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.70-7.86 (m, 6H), 7.31-7.32 (m, 1H), 5.53-5.55 (m, 1H), 5.35-5.41 (m, 1H), 5.06 (m, 1H), 4.57-4.62 (m, 1H), 3.88 (m, 1H), 1.61-1.63 (m, 3H), 0.69 (d, J=6.7 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-d1a62720a1214ec0af965953e73d409a
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

Loading…