Tetrahydrofuran → Diethyl 2-(3-(ethoxycarbonyl)-2,3-dihydrothiazol-2-yl)malonate

HRID 218229Notes

Reaction equation

HRID 218229 reaction equation
Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[S:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.C([C:14](CC)([C:19]([O-:21])=[O:20])[C:15]([O:17][Li])=[O:16])C.[CH2:24](C(CC)(C([O-])=O)C([O-])=O)[CH3:25].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O1CC[CH2:47][CH2:46]1>C(OCC)C>[CH2:5]([O:4][C:2]([N:9]1[CH:10]=[CH:11][S:7][CH:8]1[CH:14]([C:19]([O:21][CH2:46][CH3:47])=[O:20])[C:15]([O:17][CH2:24][CH3:25])=[O:16])=[O:3])[CH3:6]

Participants

8

Reactant 6

HCID 8028Tetrahydrofuran3×HCID 9256ThiazoleHCID 10928Ethyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 69515632,2-DiethylpropanedioateHCID 178506947HCID 178506947, compound

Product 1

HCID 13331878Diethyl 2-(3-(ethoxycarbonyl)-2,3-dihydrothiazol-2-yl)malonate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
23 °C

Procedure

Ethyl chloroformate (6.46 ml, 67.8 mmoles) was added dropwise to a stirred solution of thiazole (5.0 g, 58.7 mmoles) in tetrahydrofuran (113.0 ml) at about 0° C. under a nitrogen atmosphere. After about 1 hour, a freshly prepared solution of lithio diethylmalonate (To a solution of diethylmalonate (10.3 ml, 67.8 mmoles) in tetrahydrofuran (17.0 ml) was added dropwise a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (67.8 ml, 67.8 mmoles) and the mixture was stirred at 23° C. for about 10 min) was added via cannula and the mixture was stirred at room temperature for about 18 hours. The mixture was diluted with diethyl ether (60.0 ml), was washed with saturated aqueous ammonium chloride (140.0 ml) and brine (120.0 ml). The organic layer was dried over MgSO4, filtered, concentrated in vacuum and the crude product was purified by flash column chromatography on silica gel using hexanes/ethyl acetate (2:1) as the mobile phase to provide the title compound.

Workup

  1. additionwas added via cannula
  2. stirringthe mixture was stirred at room temperature for about 18 hours
  3. washwas washed with saturated aqueous ammonium chloride (140.0 ml) and brine (120.0 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customthe crude product was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-bea9c667072648e6b250f259fd125a6b
Source dataset
uspto-grants-2012_06
Patent number
US08198331B2

Reaction notes

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