Methyl iodide → 2-(Tert-butoxycarbonyl(methyl)amino)-4-methylthiazole-5-carboxylic acid

HRID 45388Notes

Reaction equation

HRID 45388 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:15]([OH:17])=[O:16])=[C:12]([CH3:14])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].IC.[C:22](=O)(O)[O-].[Na+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([CH3:22])[C:9]1[S:10][C:11]([C:15]([OH:17])=[O:16])=[C:12]([CH3:14])[N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 2756770N-Boc-amino-4-methylthiazole-5-carboxylic acid

Product 1

HCID 687014412-(Tert-butoxycarbonyl(methyl)amino)-4-methylthiazole-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(tert-butoxycarbonylamino)-4-methylthiazole-5-carboxylic acid (0.13 g, 0.50 mmol) in N,N-dimethylformamide (2.5 mL) at 0° C. was added sodium hydride (0.044 g, 1.10 mmol, 60% dispersed in mineral oil). The resultant mixture was stirred at 0° C. for 40 min, followed by the dropwise addition of iodomethane (31.2 mL, 0.50 mmol). The resultant solution was allowed to warm to ambient temperature over 18 h, followed by the addition of saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography eluting with ethyl acetate/hexanes (50/50 to 100/0) to afford 2-(tert-butoxycarbonyl(methyl)amino)-4-methylthiazole-5-carboxylic acid (0.070 g, 0.26 mmol).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography
  6. washeluting with ethyl acetate/hexanes (50/50 to 100/0)

Sources & evidence

ORD record
ord-6f6c704438684ea0bcbb020647c4af83
Source dataset
uspto-grants-2013_09
Patent number
US08541457B2

Reaction notes

Loading…