Potassium Phosphate, Tribasic → 4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

HRID 531263Notes

Reaction equation

HRID 531263 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[C:25](B4OC(C)(C)C(C)(C)O4)=[CH:24][N:23]=[C:22]([S:35][CH3:36])[N:21]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:41]1[S:45][C:44]([C:46]2[CH:54]=[CH:53][C:49]([C:50]([OH:52])=[O:51])=[CH:48][C:47]=2[CH3:55])=[N:43][C:42]=1[C:56]([CH3:59])([CH3:58])[CH3:57].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.O.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>[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[C:25]([C:41]4[S:45][C:44]([C:46]5[CH:54]=[CH:53][C:49]([C:50]([OH:52])=[O:51])=[CH:48][C:47]=5[CH3:55])=[N:43][C:42]=4[C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:24][N:23]=[C:22]([S:35][CH3:36])[N:21]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 90009110(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one2×HCID 900091134-(5-Bromo-4-tert-butylthiazol-2-yl)-3-methylbenzoic acid2×

Product 1

HCID 900093044-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acidYield 9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one (INTERMEDIATE 21, 2.0 g, 3.46 m mol), 4-(5-bromo-4-tert-butylthiazol-2-yl)-3-methylbenzoic acid (INTERMEDIATE 41, 1.350 g, 3.81 mmol), potassium phosphate (8.18 mL, 1.27 M, 10.39 m mol) in THF (5 mL) and water (5.00 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.400 g, 0.346 mmol). It was degassed, and refilled with nitrogen. The reaction mixture was heated to reflux for 2 hours to see complete conversion by LCMS. It was distributed between 100 mL of water and 300 mL of ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and the filtrate concentrated. The crude isolate was purified by silica gel chromatography, eluting with 30% ethyl acetate in hexanes to give the title compound as white solid (225 mg, 9.0% yield). LCMS (M+H)+: 725.0

Workup

  1. customIt was degassed
  2. additionrefilled with nitrogen
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 2 hours
  5. customThe organic layer was collected
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated
  9. customThe crude isolate
  10. customwas purified by silica gel chromatography
  11. washeluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-230053a3d443400cbf0446adf9c67d84
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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