Diethyl Oxalate → HCID 66633701, compound

HRID 2359925Notes

Reaction equation

HRID 2359925 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:13]=[C:14]([C:18]2[S:19][C:20]([C:24](=[O:26])[CH3:25])=[C:21]([CH3:23])[N:22]=2)[CH:15]=[N:16][CH:17]=1.[C:27](OCC)(=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29].S([O-])(O)(=O)=O.[K+]>O1CCCC1.C(OCC)C>[F:11][C:12]1[CH:13]=[C:14]([C:18]2[S:19][C:20]([C:24](=[O:26])[CH2:25][C:27](=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:21]([CH3:23])[N:22]=2)[CH:15]=[N:16][CH:17]=1

Participants

7

Reactant 4

HCID 7268Diethyl OxalateHCID 516920Potassium bisulfateHCID 2733832Lithium HexamethyldisilazideHCID 66634263HCID 66634263, compound

Product 1

HCID 66633701HCID 66633701, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Under argon, lithium bis(trimethylsilyl)amide (21 ml, 1 M/L in tetrahydrofuran) was initially charged in tetrahydrofuran (150 ml). At −78° C., 1-[2-(5-fluoropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]ethanone (5.0 g, 21 mmol, prepared analogously to Biorg. & Med. Chem. Lett 1056 (2007) and 2828 (2010)) dissolved in diethyl ether was slowly added dropwise and the reaction mixture was stirred for 2 h. Diethyl oxalate (3.1 g, 21 mmol) dissolved in ether was added dropwise and the reaction mixture was stirred at room temperature for 16 h. Subsequently, potassium hydrogensulphate solution (5%) was added and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried and the solvent was removed under reduced pressure. This gave 7.1 g (99% of theory) of ethyl 4-[2-(5-fluoropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]-2,4-dioxobutanoate.

Workup

  1. additionwas slowly added dropwise
  2. additionwas added dropwise
  3. stirringthe reaction mixture was stirred at room temperature for 16 h
  4. extractionthe mixture was extracted repeatedly with ethyl acetate
  5. customThe combined organic phases were dried
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-e229039c6af945e59573e071a23888ed
Source dataset
uspto-grants-2014_04
Patent number
US08686004B2

Reaction notes

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