Ethyl bromoacetate → HCID 18388310, compound

HRID 2296790Notes

Reaction equation

HRID 2296790 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14].[CH3:18][S:19][C:20](SC)=[C:21]1[C:26](=[O:27])[CH2:25][CH2:24][CH2:23][C:22]1=O.[Cl-].[NH4+].[O:33]1CCCC1>C(OCC)C.O>[CH3:18][S:19][C:20]1[O:33][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:22]2[CH2:23][CH2:24][CH2:25][C:26](=[O:27])[C:21]=12

Participants

8

Reactant 5

HCID 7748Ethyl bromoacetateHCID 8028Tetrahydrofuran3×HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 18388305HCID 18388305, compound

Product 1

HCID 18388310HCID 18388310, compoundYield 14.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

Lithium bis(trimethylsilyl)amide (1.0 M hexane solution, 154.0 ml) was added dropwise to tetrahydrofuran (THF) (265 ml) at −78° C. in a nitrogen stream over a period of 25 minutes. A solution of ethyl bromoacetate (25.71 g) in THF (50 ml) was then added dropwise at −78° C. ver a period of 15 minutes; a solution of 2-[bis(methylthio)methylene]cyclohexane-1,3-dione (25.62 g) in THF (240 ml) was further added drop by drop at −78° C. over a period of 30 minutes. After the reaction mixture was stirred at −78° C. for 1 hour and at room temperature for hours, it was poured over an ice cooled saturated aqueous solution of ammonium chloride (1,250 ml) and stirred at room temperature for 15 minutes. The organic layer was separated; the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (2:1, v/v) to yield an oily substance. The oily substance obtained was dissolved in diethyl ether (250 ml); a boron trifluoride-diethyl ether complex (25.21 g) was added at room temperature. After the reaction mixture was stirred at room temperature for 1 hour, it was poured over water (500 ml); the organic layer was separated; the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:3, v/v) to yield ethyl 4,5,6,7-tetrahydro-3-methylthio-4-oxobenzo[c]furan-1-carboxylate (4.41 g, 14.6%), which was then recrystallized from ethyl acetate-hexane. Colorless plates. Melting point 123-124° C.

Workup

  1. stirringstirred at room temperature for 15 minutes
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washwashed with water
  5. dry with materialdried (MgSO4)
  6. distillationafter which the solvent was distilled off
  7. washeluted with ethyl acetate-hexane (2:1
  8. customv/v) to yield an oily substance
  9. customThe oily substance obtained
  10. additiona boron trifluoride-diethyl ether complex (25.21 g) was added at room temperature
  11. stirringAfter the reaction mixture was stirred at room temperature for 1 hour
  12. customthe organic layer was separated
  13. extractionthe aqueous layer was extracted with ethyl acetate
  14. washwashed with water
  15. dry with materialdried (MgSO4)
  16. distillationafter which the solvent was distilled off
  17. washeluted with ethyl acetate-hexane (1:3

Sources & evidence

ORD record
ord-ce184b72cb0d45699cbc835e9e35f330
Source dataset
uspto-grants-2002_12
Patent number
US06489351B1

Reaction notes

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