Ethyl bromoacetate → HCID 10794469, compound

HRID 1532725Notes

Reaction equation

HRID 1532725 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][O:15][C:16]1[CH:43]=[CH:42][C:19]([CH2:20][CH:21]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])=[CH:18][CH:17]=1.[H-].[Na+].Br[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49].S([O-])(O)(=O)=O.[Na+]>O1CCCC1.O>[CH2:51]([O:50][C:48]([CH2:47][C:21]([CH2:20][C:19]1[CH:42]=[CH:43][C:16]([O:15][CH2:14][CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[O:6][C:2]=2[CH3:1])=[CH:17][CH:18]=1)([C:32]([O:34][CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:33])[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:49])[CH3:52]

Participants

7

Reactant 4

HCID 7748Ethyl bromoacetate2×HCID 24758Sodium hydride3×HCID 516919Sodium BisulfateHCID 10745722HCID 10745722, compound

Product 1

HCID 10794469HCID 10794469, compoundYield 101%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Dibenzyl 2-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]malonate (26.0 g, 45.2 mmol) synthesized according to the method described in WO95/18125 was dissolved in tetrahydrofuran (250 ml), and sodium hydride (60% in oil, 2.2 g, 54.2 mmol) was added at 0° C., which was followed by stirring at room temperature for 30 min. To the reaction mixture was added a solution of ethyl bromoacetate (15.3 ml, 135.6 mmol) in tetrahydrofuran (50 ml) at room temperature. After stirring for 1 hr, sodium hydride (60% in oil, 1.1 g, 27.1 mmol) and ethyl bromoacetate (5.1 ml, 45.2 mmol) were added. After stirring for 1 hr, sodium hydride (60% in oil, 2.2 g, 54.2 mmol) was added and the mixture was stirred for 1 hr. Water and 1N aqueous sodium hydrogensulfate solution were added to the reaction mixture and extracted three times with ethyl acetate (200 ml). The extracted organic layers were combined, washed with brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (developing solvent; hexane:ethyl acetate=5:1→3:1) to give the title compound (30.2 g, yield 100%) as an oil.

Workup

  1. stirringAfter stirring for 1 hr
  2. stirringAfter stirring for 1 hr
  3. stirringthe mixture was stirred for 1 hr
  4. extractionextracted three times with ethyl acetate (200 ml)
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (developing solvent; hexane:ethyl acetate=5:1→3:1)

Sources & evidence

ORD record
ord-6aac1a5cdd7d44ed8a77f848d42c752d
Source dataset
uspto-grants-2001_03
Patent number
US06204277B1

Reaction notes

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