Potassium Carbonate → methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 1508598Notes

Reaction equation

HRID 1508598 reaction equation
[F:1][C:2]([F:34])([F:33])[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](Br)=[CH:24][CH:23]=[C:22]([N:27]4[CH:31]=[CH:30][CH:29]=[N:28]4)[N:21]=3)[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]2[CH:48]=[CH:47][C:46]([C:49]([O:51][CH3:52])=[O:50])=[CH:45][C:44]=2[CH3:53])=[CH:39][C:38]=1B1OC(C)(C)C(C)(C)O1.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]>[F:1][C:2]([F:34])([F:33])[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:38]4[CH:39]=[C:40]([C:43]5[CH:48]=[CH:47][C:46]([C:49]([O:51][CH3:52])=[O:50])=[CH:45][C:44]=5[CH3:53])[CH:41]=[CH:42][C:37]=4[O:36][CH3:35])=[CH:24][CH:23]=[C:22]([N:27]4[CH:31]=[CH:30][CH:29]=[N:28]4)[N:21]=3)[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57692976HCID 57692976, compoundHCID 86704645(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86704646methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylateYield 69.2%

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(1H-pyrazol-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (100 mg, 0.182 mmol) in THF (0.91 mL) was added methyl 4′-methoxy-2-methyl-3′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (84 mg, 0.218 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (17.8 mg, 0.027 mmol), and potassium carbonate (2 M in water, 0.273 mL, 0.546 mmol). The system was flushed with nitrogen, capped, and stirred at room temperature overnight. The reaction was diluted with ethyl acetate and the organic was washed with water (2×), brine, dried (Na2SO4), filtered, and concentrated. The crude material was purified by column chromatography to yield methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (91.4 mg, 0.126 mmol). LCMS calc.=725.2. found=725.3.

Workup

  1. customThe system was flushed with nitrogen
  2. customcapped
  3. additionThe reaction was diluted with ethyl acetate
  4. washthe organic was washed with water (2×), brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-fafad854e4374ac6b78feadbe9e5c278
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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