Tetrahydrofuran → 2-Cyclohexylmethyl-benzothiazole-6-carbonitrile

HRID 2041440Notes

Reaction equation

HRID 2041440 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. Purify 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
  10. customPurify the residue by chromatography on silica gel eluting sequentially with hexane/EtOAc (1:0 to 4:1 gradient)

Sources & evidence

ORD record
ord-58e513b40a0b46ef9536849d5a087074
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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