(Prop-1-en-2-yl)boronic acid → HCID 24969647, compound

HRID 604643Notes

Reaction equation

HRID 604643 reaction equation
[F:1][C:2]([F:41])([F:40])[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:26]4[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[C:29]([F:35])=[CH:28][C:27]=4[O:36][CH3:37])=[CH:24][CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:42](B(O)O)([CH3:44])=[CH2:43]>C1COCC1.C(=O)([O-])[O-].[K+].[K+]>[F:1][C:2]([F:41])([F:40])[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:26]4[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[C:29]([F:35])=[CH:28][C:27]=4[O:36][CH3:37])=[CH:24][CH:23]=[C:22]([C:42]([CH3:44])=[CH2:43])[N:21]=3)[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 2

HCID 10855372(Prop-1-en-2-yl)boronic acidHCID 24969552HCID 24969552, compound

Product 1

HCID 24969647HCID 24969647, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 11430Potassium CarbonateSolvent

Procedure

A mixture of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-chloro-3-(4-fluoro-5-isopropyl-2-methoxyphenyl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (EXAMPLE 18) (43 mg, 0.071 mmol) and isopropenyl boronic acid (Molander, G. A.; et. al. J. Am. Chem. Soc. 2003, 125, 11148-11149) (122 mg, 1.42 mmol) in THF (3 mL) and 1N aqueous potassium carbonate (3 mL). 1,1-Bis(di-t-Bu-phosphino)ferrocene palladium dichloride (4.6 mg, 0.0071 mmol) was heated at 80° C. for 4 h in a sealed tube. The mixture was cooled to room temperature and filtered through Celite. The filtrate was diluted with water and extracted with EtOAc (3×). The combined organic extracts were washed with brine (1×), dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si, hexanes/EtOAc) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropenylpyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=611.2; found=611.2 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers) δ 7.88 (s, 1H); 7.75 (s, 2H); 7.51 (s, 2H); 7.04 (br, s, 0.5H); 6.99 (br, s, 0.5H); 6.71 (s, 0.5H); 6.69 (s, 0.5H); 5.98 (s, 1H); 5.68 (br, s, 0.5H); 5.66 (br, s, 0.5H); 5.37 (m, 1H); 5.00-4.74 (m, 1H); 4.56-4.20 (m, 1H); 4.20-3.90 (m, 1H); 3.77 (s, 3H); 3.25-3.18 (m, 1H); 2.28 (s, 3H); 1.32-1.22 (m, 6H); 0.74 (br, s, 1.5H); 0.64 (br, s, 1.5H).

Workup

  1. filtrationfiltered through Celite
  2. additionThe filtrate was diluted with water
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organic extracts were washed with brine (1×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (Si, hexanes/EtOAc)

Sources & evidence

ORD record
ord-d92bdbeb471c41429307f782c194a902
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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