Potassium Carbonate → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(2-isopropenyl-1,3-thiazol-4-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1028587Notes

Reaction equation

HRID 1028587 reaction equation
Br[C:2]1[N:3]=[C:4]([C:7]([CH3:9])=[CH2:8])[S:5][CH:6]=1.[F:10][C:11]([F:50])([F:49])[C:12]1[CH:13]=[C:14]([C@H:22]2[O:26][C:25](=[O:27])[N:24]([CH2:28][C:29]3[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][C:30]=3B3OC(C)(C)C(C)(C)O3)[C@H:23]2[CH3:48])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[F:50][C:11]([F:10])([F:49])[C:12]1[CH:13]=[C:14]([C@H:22]2[O:26][C:25](=[O:27])[N:24]([CH2:28][C:29]3[CH:34]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:32]=[CH:31][C:30]=3[C:2]3[N:3]=[C:4]([C:7]([CH3:9])=[CH2:8])[S:5][CH:6]=3)[C@H:23]2[CH3:48])[CH:15]=[C:16]([C:18]([F:19])([F:21])[F:20])[CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 112294714-Bromo-2-isopropenyl-1,3-thiazoleHCID 57704783(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

Product 1

HCID 11505288(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(2-isopropenyl-1,3-thiazol-4-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

In a tube were placed 4-bromo-2-isopropenyl-1,3-thiazole (20 mg, 0.097 mmol), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (29.4 mg, 0.0492 mmol), THF (340 μL), 1M aqueous K2CO3 (340 μL), and 1,1-bis(di-t-butylphosphino)ferrocene palladium chloride (3.2 mg, 4.9×10−3 mmol). The mixture was degassed with N2. The tube was sealed and heated at 100° C. for 1.5 hours. The reaction was then cooled to room temperature, diluted with EtOAc (50 mL), and 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 25% EtOAc/hexanes) and then by PTLC (90% CH2Cl2/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(2-isopropenyl-1,3-thiazol-4-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.16 (15% EtOAc/hexanes). LCMS=595.1 (M+1)+. 1H NMR (CD2Cl2, 500 MHz) δ 7.90 (s, 1H), 7.64-7.76 (m, 5H), 7.38 (s, 1H), 5.89 (s, 1H), 5.60 (d, J=8.1 Hz, 1H), 5.37 (d, J=1.2 Hz, 1H), 4.99 (d, J=16.0 Hz, 1H), 4.66 (d, J=16.0 Hz, 1H), 3.94 (m, 1H), 2.25 (s, 3H), 0.59 (d, J=6.4 Hz, 3H).

Workup

  1. customIn a tube were placed
  2. customThe mixture was degassed with N2
  3. customThe tube was sealed
  4. temperatureThe reaction was then cooled to room temperature
  5. additiondiluted with EtOAc (50 mL)
  6. washwashed 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 (5 to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-38f5c287e38e45ce85d13cb992044fe1
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

Loading…