Ethanol → HCID 59580505, compound

HRID 1470425Notes

Reaction equation

HRID 1470425 reaction equation
[F:1][C:2]1[C:3](B(O)O)=[N:4][CH:5]=[CH:6][CH:7]=1.C(O)C.C([O-])([O-])=O.[K+].[K+].Br[C:21]1[S:22][C:23]([N:26]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:24][N:25]=1>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.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([C:21]2[S:22][C:23]([N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])=[CH:24][N:25]=2)[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 53401125(3-Fluoropyridin-2-yl)boronic acidHCID 59580599HCID 59580599, compound

Product 1

HCID 59580505HCID 59580505, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a 3-neck round bottom flask was added fluoropyridine boronic acid (4.55 g, 32.3 mmol), ethanol (54 mL), and aqueous K2CO3 solution (27 mL, 2.0 M, 53.8 mmol), followed by 50 mL toluene. To this mixture was added di(tert-butyl) 2-bromo-1,3-thiazol-5-ylimidodicarbonate (10.2 g, 26.9 mmol). Next, tetrakis(triphenylphosphine)palladium(0) (6.2 g, 5.4 mmol) was added in one portion. The flask was fitted with a reflux condenser and was heated to reflux. After 45 minutes, the reaction was cooled in an ice bath and partitioned between aqueous saturated NaHCO3 and ethyl acetate. The layers were separated and the aqueous layer was extracted once with ethyl acetate. The combined organics were washed once with brine, dried over MgSO4, filtered, and then concentrated. This solid was triturated with 20% ethyl acetate/hexanes. The solids were filtered off and the filtrate evaporated to provide a residue which was purified via silica gel column chromatography (0 to 100% ethyl acetate/hexanes) to afford the desired product as an off-white solid (7.74 g, 73% yield): mp 94-96° C.; 1H NMR (300 MHz, CDCl3) δ 8.91 (app t, J=1.3 Hz, 1H), 8.52 (d, J=3.0 Hz, 1H), 7.96 (ddd, J=9.2, 3.0, 1.8 Hz, 1H), 7.66 (s, 1H), 1.48 (s, 18H); ESIMS m/z 396 (M+1).

Workup

  1. customThe flask was fitted with a reflux condenser
  2. temperaturewas heated to reflux
  3. temperaturethe reaction was cooled in an ice bath
  4. custompartitioned between aqueous saturated NaHCO3 and ethyl acetate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted once with ethyl acetate
  7. washThe combined organics were washed once with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThis solid was triturated with 20% ethyl acetate/hexanes
  12. filtrationThe solids were filtered off
  13. customthe filtrate evaporated
  14. customto provide a residue which
  15. customwas purified via silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a45863f2bcbd43b8a223592cf082b112
Source dataset
uspto-grants-2015_04
Patent number
US09006446B2

Reaction notes

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