Thiazole → Ethyl (E)-4-[2-(5,5-dimethyl-8-(thiazol-2-yl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoate

HRID 1953865Notes

Reaction equation

HRID 1953865 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[CH3:11][C:12]1([CH3:43])[CH2:21][CH:20]=[C:19](OS(C(F)(F)F)(=O)=O)[C:18]2[CH:17]=[C:16](/[CH:30]=[CH:31]/[C:32]3[CH:42]=[CH:41][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][CH:33]=3)[CH:15]=[CH:14][C:13]1=2.[NH4+].[Cl-]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:43][C:12]1([CH3:11])[CH2:21][CH:20]=[C:19]([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[C:18]2[CH:17]=[C:16](/[CH:30]=[CH:31]/[C:32]3[CH:33]=[CH:34][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:41][CH:42]=3)[CH:15]=[CH:14][C:13]1=2

Participants

8

Reactant 4

HCID 9256ThiazoleHCID 25517Ammonium ChlorideHCID 19695065ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6-dihydronaphthalen-2-yl)ethenyl]benzoate2×HCID 178418339Butyllithium

Product 1

HCID 15887382Ethyl (E)-4-[2-(5,5-dimethyl-8-(thiazol-2-yl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a cold (-78° C.) solution of thiazole (0.38 g (0.10 mL, 1.4 mmol) in THF (2.0 mL) was added n-butyl lithium (1.6 M solution in hexanes, 0.5 mL, 0.8 mmol) and stirred for 30 min. To this solution was added 0.176 g (1.3 mmol) of zinc chloride in 3.0 mL of tetrahydrofuran and stirred for 45 min. The resulting turbid solution was transferred, via cannula, to a flask containing a mixture of 0.17 g (0.35 mmol) of ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6-dihydronaphthalen-2-yl)ethenyl]benzoate (Compound A9) and 15 mg (0.01 mmol) of tetrakis(triphenylphosphine)palladium(0) in 3.0 mL of tetrahydrofuran. The reaction mixture was stirred for 1 h at ambient temperature and 1.5 h at 55° C. The reaction mixture was treated with aqueous NH4Cl, and extracted with EtOAc (2 x). The combined organic layer was washed with brine and dried (MgSO4). The solvent was removed under reduced pressure and the crude product was purified by flash chromatography (silica, 20% ethyl acetate in hexane) to afford the title compound as a white solid.

Workup

  1. stirringstirred for 45 min
  2. customThe resulting turbid solution was transferred, via cannula, to a flask
  3. additioncontaining
  4. stirringThe reaction mixture was stirred for 1 h at ambient temperature and 1.5 h at 55° C
  5. extractionextracted with EtOAc (2 x)
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customThe solvent was removed under reduced pressure
  9. customthe crude product was purified by flash chromatography (silica, 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-48389fe127be46b1ab8d895bf90d6a25
Source dataset
uspto-grants-2000_09
Patent number
US06117987

Reaction notes

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