Tetrahydrofuran → 2-Cyclohexylmethyl-benzothiazole-6-carbonitrile

HRID 911573Notes

Reaction equation

HRID 911573 reaction equation
Br[C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[CH:7][C:5]=2[N:6]=1.C1COCC1.[Br-].[CH:19]1([CH2:25][Zn+])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN1CCCC1=O>[CH:19]1([CH2:25][C:2]2[S:3][C:4]3[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

7

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 252588342-Bromobenzo[d]thiazole-6-carbonitrileHCID 178419774HCID 178419774, compound

Product 1

HCID 667067722-Cyclohexylmethyl-benzothiazole-6-carbonitrileYield 57%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

Place 2-bromo-benzothiazole-6-carbonitrile (0.2 g, 0.96 mmol), anhydrous THF (3 mL), 1-methyl-2-pyrrolidinone (3 mL), tetrabutylammonium iodide (1.1 g, 2.89 mmol), tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.09 mmol) and [1,1′-bis(diphenylphosphino)ferrocine]dichloropalladium (II) (11 mg, 0.09 mmol) in a flask. Add 0.5M cyclohexylmethylzinc bromide in THF (3.8 mL, 1.92 mmol) to the mixture, degas 3 times by partially evacuating the atmosphere and flushing with nitrogen and stir the reaction mixture at 80° C. for 2 h. Cool the reaction mixture to room temperature, dilute with EtOAc (10 mL) and wash with brine (10 mL). Dry the organic layer over anhydrous Na2SO4, filter and concentrate in vacuo. Purity the residue by chromatography on silica gel eluting sequentially with hexane/EtOAc (1:0 to 4:1 gradient) to obtain the desired intermediate as a yellow solid (140 mg, 57%). GC-MS m/z: 256 (M+).

Workup

  1. customdegas 3 times
  2. customby partially evacuating the atmosphere
  3. customflushing with nitrogen
  4. temperatureCool the reaction mixture to room temperature
  5. additiondilute with EtOAc (10 mL)
  6. washwash with brine (10 mL)
  7. dry with materialDry the organic layer over anhydrous Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-a3e65b8c4beb4fda9756db4a3b5ff877
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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