2,6-Lutidine → Ethyl 2-[(Cbz-amino)methyl]thiazole-4-carboxylate

HRID 736705Notes

Reaction equation

HRID 736705 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][O:8][C:9]([NH:11][CH2:12][C:13]([NH2:15])=[S:14])=[O:10])=[CH:3][CH:2]=1.C(=O)([O-])O.[K+].C([CH:23](Br)[C:24](=O)[C:25]([O-:27])=[O:26])C.F[C:31](F)(F)[C:32](OC(=O)C(F)(F)F)=O.N1C(C)=CC=CC=1C>COCCOC>[CH2:7]([O:8][C:9]([NH:11][CH2:12][C:13]1[S:14][CH:23]=[C:24]([C:25]([O:27][CH2:31][CH3:32])=[O:26])[N:15]=1)=[O:10])[C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 9845Trifluoroacetic anhydrideHCID 516893Potassium BicarbonateHCID 2756641N-Benzyloxycarbonylglycine thioamideHCID 21948992Ethylbromopyruvate

Product 1

HCID 10403722Ethyl 2-[(Cbz-amino)methyl]thiazole-4-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of N-benzyloxycarbonylglycine thioamide (1.49 g, 6.64 mmol) in 1,2-dimethoxyethane (25 mL) was added potassium hydrogen carbonate (2.66 g, 26.56 mmol) and ethylbromopyruvate (3.47 mL, 27.54 mmol) at −20° C. and the mixture stirred at −20° C. overnight. The mixture was filtered through a pad of celite and the filtrate was concentrated and the residue was dissolved in 1,2-dimethoxyethane. After cooling to −20° C., a solution of trifluoroacetic anhydride (2.85 mL, 20.52 mmol) and 2,6-lutidine (5.14 mL, 44.29 mmol) in 1,2-dimethoxyethane (10 mL) was added dropwise over 10 minutes. After stirring for 45 minutes, the solution was concentrated and partitioned between chloroform and water. The organic layer was concentrated and the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes to provide the title product (1.8 g, 85%): MS (DCI/NH3) m/z 321 (M+H)+.

Workup

  1. filtrationThe mixture was filtered through a pad of celite
  2. concentrationthe filtrate was concentrated
  3. dissolutionthe residue was dissolved in 1,2-dimethoxyethane
  4. temperatureAfter cooling to −20° C.
  5. stirringAfter stirring for 45 minutes
  6. concentrationthe solution was concentrated
  7. custompartitioned between chloroform and water
  8. concentrationThe organic layer was concentrated
  9. customthe residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-27159bec95eb4207a44c9ba8d994e6d7
Source dataset
uspto-grants-2009_09
Patent number
US07595406B2

Reaction notes

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