Citric Acid → 2-Isopropylthiazole-4-carbaldehyde

HRID 1859509Notes

Reaction equation

HRID 1859509 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[C:8]([CH:11]([CH3:13])[CH3:12])[S:9][CH:10]=1)=O)C.CC(C[AlH]CC(C)C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH:11]([C:8]1[S:9][CH:10]=[C:6]([CH:4]=[O:3])[N:7]=1)([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14487Diisobutylaluminum hydride2×HCID 10535999Ethyl 2-isopropylthiazole-4-carboxylate

Product 1

HCID 27631922-Isopropylthiazole-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2.7 g (13 mmol) of 2-isopropyl-thiazole-4-carboxylic acid ethyl ester (J. Med. Chem., 1998:602-617) in CH2Cl2 (50 mL) was cooled to −78° C. under nitrogen and treated dropwise with DIBAL (15 mL of 1.0 M in CH2Cl2; 15 mmol). The mixture was stirred at low temperature for 45 minutes and then treated with another 15 mL of DIBAL. The solution was stirred for 1 hour at −78° C. Five percent citric acid was added, and the mixture was extracted with EtOAc (3×100 mL). The combined extracts were washed with brine, dried (MgSO4), and concentrated. Chromatography of the residue over silica gel, eluting with 3:1 hexane:EtOAc, gave the title compound.

Workup

  1. stirringThe solution was stirred for 1 hour at −78° C
  2. extractionthe mixture was extracted with EtOAc (3×100 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washChromatography of the residue over silica gel, eluting with 3:1 hexane

Sources & evidence

ORD record
ord-b328fad12b2f471293c4dd6c48bb9353
Source dataset
uspto-grants-2003_03
Patent number
US06528510B1

Reaction notes

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