Diethyl Malonate → 4-Tert-butyl-2-[5-(2,2-diethoxycarbonylethyl)benzofuran-2-yl]thiazole

HRID 487701Notes

Reaction equation

HRID 487701 reaction equation
C[Mg]Br.[C:4]([O:12][CH2:13][CH3:14])(=[O:11])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[C:15]([C:19]1[N:20]=[C:21]([C:24]2[O:25][C:26]3[CH:32]=[CH:31][C:30]([CH2:33]Cl)=[CH:29][C:27]=3[CH:28]=2)[S:22][CH:23]=1)([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])O.[Na+]>O1CCCC1>[C:15]([C:19]1[N:20]=[C:21]([C:24]2[O:25][C:26]3[CH:32]=[CH:31][C:30]([CH2:33][CH:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:4]([O:12][CH2:13][CH3:14])=[O:11])=[CH:29][C:27]=3[CH:28]=2)[S:22][CH:23]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 516892Sodium BicarbonateHCID 19603727HCID 19603727, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 190926974-Tert-butyl-2-[5-(2,2-diethoxycarbonylethyl)benzofuran-2-yl]thiazoleYield 118%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methylmagnesium bromide in tetrahydrofuran (1N, 15 ml) was added to diethyl malonate (7.33 g) at 0° C. for 10 minutes. The mixture was stirred for 2 hours at ambient temperature. To the mixture, 4-tert-butyl-2-(5-chloromethylbenzofuran-2-yl)thiazole (3.50 g) was added and stirred for 23 hours at 45° C. The resulting mixture was concentrated under reduced pressure and added to the solution of 4N hydrogen chloride in ethyl acetate. The resulting precipitates were collected by filtration and washed with n-hexane and diisopropyl ether to give the salt. The salt was added to the aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give 4-tert-butyl-2-[5-(2,2-diethoxycarbonylethyl)benzofuran-2-yl]thiazole (5.80 g).

Workup

  1. stirringstirred for 23 hours at 45° C
  2. concentrationThe resulting mixture was concentrated under reduced pressure
  3. additionadded to the solution of 4N hydrogen chloride in ethyl acetate
  4. customThe resulting precipitates
  5. filtrationwere collected by filtration
  6. washwashed with n-hexane and diisopropyl ether
  7. customto give the salt
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-86ec82fcde99464caebd515e437cd654
Source dataset
uspto-grants-1994_03
Patent number
US05296495

Reaction notes

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