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

HRID 410389Notes

Reaction equation

HRID 410389 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-1c11383ee66248e393d3b53507a6a7dc
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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