18-Crown-6 → tert-Butyl 4-(3-chloro-4-cyanoisothiazol-5-yl)phenylcarbamate

HRID 871028Notes

Reaction equation

HRID 871028 reaction equation
[Cl:1][C:2]1[C:6]([C:7]#[N:8])=[C:5](Cl)[S:4][N:3]=1.[C:10]([O:14][C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[F-].[K+].C1OCCOCCOCCOCCOCCOC1>C1(C)C=CC=CC=1.O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[C:6]([C:7]#[N:8])=[C:5]([C:21]2[CH:20]=[CH:19][C:18]([NH:17][C:15](=[O:16])[O:14][C:10]([CH3:12])([CH3:11])[CH3:13])=[CH:23][CH:22]=2)[S:4][N:3]=1

Participants

9

Reactant 4

HCID 2855718-Crown-6HCID 305706Dichloro-1,2-thiazole-4-carbonitrileHCID 522689Potassium FluorideHCID 3613184(4-Boc-Aminophenyl)Boronic Acid

Product 1

HCID 86689222tert-Butyl 4-(3-chloro-4-cyanoisothiazol-5-yl)phenylcarbamateYield 85%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3,5-dichloroisothiazole-4-carbonitrile (5.37 g, 30 mmol), 4-(tert-butoxycarbonylamino)phenylboronic acid (14.22 g, 60 mmol), potassium fluoride (6.11 g, 105 mmol), 18-crown-6 (3.96 g, 15 mmol), and palladium acetate (337 mg, 1.5 mmol) in toluene (250 ml) was heated at reflux for 6 hours. The reaction was cooled to room temperature and the mixture was diluted with water and EtOAc. Layers were separated and the aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with brine and dried with MgSO4, filtered, and concentrated. The crude product was purified by flash silica gel column eluted with 5-15% EtOAc in hexanes to obtain the title compound as a white crystalline solid (8.55 g, 85%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6 hours
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash silica gel column
  10. washeluted with 5-15% EtOAc in hexanes

Sources & evidence

ORD record
ord-2d58573f3e234fcba77dbba2e124368f
Source dataset
uspto-grants-2015_03
Patent number
US08969583B2

Reaction notes

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