Potassium Carbonate → methyl 4-{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-thiazol-4-yl}-3-methylbenzoate

HRID 607125Notes

Reaction equation

HRID 607125 reaction equation
[F:1][C:2]([F:38])([F:37])[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](Br)[N:34]=3)[C@H:14]2[CH3:36])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:39][C:40]1[CH:41]=[C:42]([CH:47]=[CH:48][C:49]=1B1OC(C)(C)C(C)(C)O1)[C:43]([O:45][CH3:46])=[O:44].C([O-])([O-])=O.[K+].[K+]>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].C1COCC1>[F:1][C:2]([F:38])([F:37])[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]([C:49]4[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][C:40]=4[CH3:39])[N:34]=3)[C@H:14]2[CH3:36])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol esterHCID 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

Product 1

HCID 86630553methyl 4-{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-thiazol-4-yl}-3-methylbenzoate

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

In a tube were placed (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 (46.0 mg, 0.073 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (30 mg, 0.11 mmol), 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (5 mg, 7.3×10−3 mmol), THF (1 mL) and 1M K2CO3 (1 mL, 1 mmol). The mixture was degassed with N2, the tube was sealed, and the reaction was heated to 90° 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 40% EtOAc/hexanes) afforded methyl 4-{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-thiazol-4-yl}-3-methylbenzoate. Rf=0.29 (25% EtOAc/hexanes). LCMS=702.9 (M+1)+. 1H NMR (CDCl3, 600 MHz) δ 7.97 (s, 1H), 7.92 (dd, J=8.0, 1.4 Hz, 1H), 7.85-7.86 (m, 3H), 7.69-7.72 (m, 4H), 7.53 (s, 1H), 5.66 (d, J=8.0 Hz, 1H), 5.11 (d, J=16.2 Hz, 1H), 4.95 (d, J=16.2 Hz, 1H), 4.11 (m, 1H), 3.93 (s, 3H), 2.54 (s, 3H), 0.60 (d, J=6.6 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 cooled to room temperature
  5. additiondiluted with EtOAc (30 mL)
  6. washThe organic layer was washed with water and brine (10 mL) each,
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the residue by flash chromatography on silica gel (5 to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-abf916c33a8b46fa8e6a5794e4d50482
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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