Potassium Carbonate → HCID 178490599, compound

HRID 1508593Notes

Reaction equation

HRID 1508593 reaction equation
Br[C:2]1[C:3]([CH2:14][N:15]2[C@@H:19]([CH3:20])[C@@H:18]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([F:31])[CH:22]=3)[O:17][C:16]2=[O:32])=[N:4][C:5]([N:8]2[CH2:11][C:10]([F:13])([F:12])[CH2:9]2)=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([C@H:47]2[CH2:52][CH2:51][C@H:50]([C:53]([O:55][CH3:56])=[O:54])[CH2:49][CH2:48]2)=[CH:43][C:42]=1B1OC(C)(C)C(C)(C)O1>[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:12][C:10]1([F:13])[CH2:11][N:8]([C:5]2[N:4]=[C:3]([CH2:14][N:15]3[C@@H:19]([CH3:20])[C@@H:18]([C:21]4[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([F:31])[CH:22]=4)[O:17][C:16]3=[O:32])[C:2]([C:46]3[CH:45]=[C:44]([C@H:47]4[CH2:48][CH2:49][C@H:50]([C:53]([O:55][CH3:56])=[O:54])[CH2:51][CH2:52]4)[CH:43]=[CH:42][C:41]=3[O:40][CH3:39])=[CH:7][CH:6]=2)[CH2:9]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86704639(4S,5R)-3-{[3-bromo-6-(3,3-difluoroazetidin-1-yl)pyridin-2-yl]methyl}-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-oneHCID 178490598HCID 178490598, compound2×

Product 1

HCID 178490599HCID 178490599, compound

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(4S,5R)-3-{[3-bromo-6-(3,3-difluoroazetidin-1-yl)pyridin-2-yl]methyl}-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (530.8 mg, 1.012 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (66.0 mg, 0.101 mmol), potassium carbonate (1.519 ml, 3.04 mmol), methyl trans-4-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclohexanecarboxylate (INTERMEDIATE 7) (436 mg, 1.164 mmol) and THF (6 ml) were sealed in a reaction vessel and placed in a 90° C. oil bath for 4 hrs. LCMS indicated complete consumption of the starting material and formation of the desired product. Volatiles were removed under reduced pressure. The resulting pot residue was worked up with brine/ethyl acetate. The combined extracts were dried over Na2SO4, filtered and evaporated to afford a dark mixture. This mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 40%). Related fractions were pooled and evaporated in vacuo to afford a brown solid foam of 507 mg as the titled compound. LCMS calc.=691.25. found=692.49 (M+1)+.

Workup

  1. customplaced in a 90° C.
  2. customfor 4 hrs
  3. customconsumption of the starting material and formation of the desired product
  4. customVolatiles were removed under reduced pressure
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto afford a dark mixture
  9. customThis mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge)
  10. washThe column was eluted by an ethyl acetate/hexanes mixture (0% to 40%)
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-cf9cac300efa4a1f84ed6fbb076ebc8f
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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