Potassium Carbonate → HCID 90009140, compound

HRID 531233Notes

Reaction equation

HRID 531233 reaction equation
Br[C:2]1[C:3]([CH2:10][N:11]2[C@@H:15]([CH3:16])[C@@H:14]([C:17]3[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=3)[O:13][C:12]2=[O:28])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.[Cl:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[C:33]([O:36][CH3:37])=[N:34][CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.[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]>[Cl:29][C:30]1[CH:31]=[C:32]([C:2]2[C:3]([CH2:10][N:11]3[C@@H:15]([CH3:16])[C@@H:14]([C:17]4[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=4)[O:13][C:12]3=[O:28])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=2)[C:33]([O:36][CH3:37])=[N:34][CH:35]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 509892825-Chloro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90009169HCID 90009169, compound2×

Product 1

HCID 90009140HCID 90009140, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (4S,5R)-3-{[5-bromo-2-(methylsulfanyl)pyrimidin-4-yl]methyl}-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 10, 263 mg, 0.548 mmol) in THF (3.0 mL) was added 5-chloro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (221 mg, 0.821 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (17.8 mg, 0.027 mmol), and aqueous potassium carbonate (0.821 mL, 2.0 M). The mixture was degassed, flushed with nitrogen and heated to 40° C. for 18 hours. The reaction was diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography to afford (4S,5R)-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylsulfanyl)pyrimidin-4-yl]methyl}-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (211 mg, 0.389 mmol). LCMS (M+H)+: 543.0.

Workup

  1. customThe mixture was degassed
  2. customflushed with nitrogen
  3. additionThe reaction was diluted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5a21e6efc80d48b4ab64d080e039dc76
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

Loading…