Water → 5-(5-Bromo-1,3-thiazol-2-yl)-2-(2-methylpropyl)benzonitrile

HRID 1942662Notes

Reaction equation

HRID 1942662 reaction equation
[CH3:1][CH:2]([CH3:21])[CH2:3][C:4]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:5]=1[C:6]#[N:7].Br[C:23]1[S:24][C:25]([Br:28])=[CH:26][N:27]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>COCCOC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:28][C:25]1[S:24][C:23]([C:9]2[CH:10]=[CH:11][C:4]([CH2:3][CH:2]([CH3:1])[CH3:21])=[C:5]([CH:8]=2)[C:6]#[N:7])=[N:27][CH:26]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 3123942,5-DibromothiazoleHCID 51358167Benzonitrile, 2-(2-methylpropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-

Product 1

HCID 584940975-(5-Bromo-1,3-thiazol-2-yl)-2-(2-methylpropyl)benzonitrileYield 59.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2-(2-methylpropyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (D59) (600 mg), 2,5-dibromo-1,3-thiazole (767 mg), and Cs2CO3 (1028 mg) in 1,2-dimethoxyethane (DME) (10 mL)/water (2 mL) stirred under nitrogen at room temperature was added PdCl2(dppf)-CH2Cl2 adduct (344 mg). The reaction mixture was sealed and heated under microwave at 120° C. for 4 h. After cooling the reaction, the mixture was diluted with ethyl acetate and filtered through silical gel. The filtrate was washed with aqueous saturated ammonium chloride and saturated brine. The organic phase was collected and dried over anhydrous sodium sulphate. The solvent was removed in vacuo to give the crude product, which was purified by column chromatography to afford 5-(5-bromo-1,3-thiazol-2-yl)-2-(2-methylpropyl)benzonitrile (D91) (400 mg). MS (ES): C14H13BrN2S requires 320. found 321.0 (M+H+).

Workup

  1. customThe reaction mixture was sealed
  2. temperatureheated under microwave at 120° C. for 4 h
  3. temperatureAfter cooling
  4. customthe reaction
  5. filtrationfiltered through silical gel
  6. washThe filtrate was washed with aqueous saturated ammonium chloride and saturated brine
  7. customThe organic phase was collected
  8. dry with materialdried over anhydrous sodium sulphate
  9. customThe solvent was removed in vacuo
  10. customto give the crude product, which
  11. customwas purified by column chromatography

Sources & evidence

ORD record
ord-d1bda75ef4b146228af169e4257fb575
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

Loading…