Sodium Carbonate → 1-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 1039879Notes

Reaction equation

HRID 1039879 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.Br[C:15]1[S:19][C:18]([C:20]2([OH:24])[CH2:23][CH2:22][CH2:21]2)=[N:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:1][C:2]1[CH:3]=[C:4]([C:15]2[S:19][C:18]([C:20]3([OH:24])[CH2:23][CH2:22][CH2:21]3)=[N:17][CH:16]=2)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27378063-Amino-5-nitrobenzeneboronic acidHCID 58456224HCID 58456224, compound

Product 1

HCID 584562421-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanolYield 92%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of commercially available (3-amino-5-nitrophenyl)boronic acid (18 g, 99 mmol) and Intermediate 1 (25.5 g, 109 mmol) in DME (360 mL) were added tetrakis(triphenyl-phosphine)palladium(0) (5.72 g, 4.95 mmol) and 2M Na2CO3(aq) (148 mL, 297 mmol), and the mixture was degassed and then heated to 85° C. for 5 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (500 mL) and filtered through Celite (ethyl acetate rinse). The filtrate was washed with brine (300 mL), dried (Na2SO4) and concentrated in vacuo. The impure material was split into two batches, and each purified by Chromatography on silica gel (70:30 to 0:100 hexanes:ethyl acetate) then the product fractions from the two purifications were combined and concentrated in vacuo to provide 26.53 g (91 mmol, 92%) of 1-[5-(3-amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol as a green solid. MS ESI: [M+H]+m/z 292.0. 1H NMR (DMSO-d6): δ 8.15 (1H, s), 7.54 (1H, s), 7.33 (1H, s), 7.14 (1H, s), 6.58 (1H, s), 6.00 (2H, s), 2.56-2.47 (2H, m), 2.39-2.29 (2H, m), 1.95-1.83 (2H, m).

Workup

  1. customthe mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe mixture was diluted with ethyl acetate (500 mL)
  4. filtrationfiltered through Celite (ethyl acetate rinse)
  5. washThe filtrate was washed with brine (300 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe impure material was split into two batches
  9. customeach purified by Chromatography on silica gel (70:30 to 0:100 hexanes:ethyl acetate)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-61a8d309d2004a8183e82790d0b54f91
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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