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

HRID 2093229Notes

Reaction equation

HRID 2093229 reaction equation
[F:1][C:2]([F:41])([F:40])[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]=3B3OC(C)(C)C(C)(C)O3)[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:43]1[S:44][CH:45]=[C:46]([Br:48])[N:47]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[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:43]3[S:44][CH:45]=[C:46]([Br:48])[N:47]=3)[C@H:14]2[CH3:39])[CH:4]=[C:3]([C:2]([F:40])([F:41])[F:1])[CH:8]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27632972,4-Dibromo-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 86630552(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(4-bromo-1,3-thiazol-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

In a tube were placed (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 (59 mg, 0.099 mmol), 2,4-dibromothiazole (60 mg, 0.247 mmol), DME (420 μL), EtOH (140 μL), and 1M Na2CO3 (296 μL, 0.296 mmol). The mixture was degassed with N2 and then Pd(PPh3)4 (5.7 mg, 4.94×10−3 mmol) was added. The mixture was degassed with N2 again, and then the tube was sealed, and the reaction was heated at 100° C. for 90 minutes. The reaction was cooled to room temperature and diluted with EtOAc (30 mL). The organic layer was washed with water and brine (10 mL) each, dried over Na2SO4, filtered and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(4-bromo-1,3-thiazol-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.33 (25% EtOAc/hexanes). LCMS=635.0 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.89 (bs, 2H), 7.78 (s, 2H), 7.75 (d, J=8.3 Hz, 1H), 7.68 (dd, J=8.1, 1.0 Hz, 1H), 7.41 (s, 1H), 5.66 (d, J=8.0 Hz, 1H), 5.02 (d, J=15.8 Hz, 1H), 4.84 (J=15.8 Hz, 1H), 4.20 (m, 1H), 0.78 (d, J=6.7 Hz, 3H).

Workup

  1. customIn a tube were placed
  2. customThe mixture was degassed with N2
  3. customThe mixture was degassed with N2 again
  4. customthe tube was sealed
  5. temperatureThe reaction was cooled to room temperature
  6. additiondiluted with EtOAc (30 mL)
  7. washThe organic layer was washed with water and brine (10 mL) each,
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5e1de94ebd684eebb716149df9631bb9
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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