Methanamine, N-methoxy-, hydrochloride (1:1) → 4-Methoxymethyl-2-phenyl-thiazole-5-carboxylic Acid Methoxy-methyl Amide

HRID 585100

Reaction equation

HRID 585100 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].[Cl-].C[Al+]C.CO[C:12]([C:14]1[S:18][C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:16][C:15]=1[CH2:25][O:26][CH3:27])=[O:13]>C(Cl)Cl>[CH3:5][O:4][N:3]([CH3:2])[C:12]([C:14]1[S:18][C:17]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:16][C:15]=1[CH2:25][O:26][CH3:27])=[O:13]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 99651204-Methoxymethyl-2-phenyl-thiazole-5-carboxylic acid methyl esterHCID 16686359Dimethylalumanylium chloride

Product 1

HCID 213547804-Methoxymethyl-2-phenyl-thiazole-5-carboxylic Acid Methoxy-methyl AmideYield 97.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N,O-dimethylhydroxylamine hydrochloride (13.3 g, 136.3 mmole, 6.0 eq) in dry CH2Cl2(250 ml) at 0° C. was treated dropwise with neat dimethylaluminum chloride (12.7 ml, 136.3 mmole, 6.0 eq) and the resulting mixture stirred at 0° C. for 2 hours then allowed to warm to RT. To this mixture was added dropwise a solution of the above-prepared 4-methoxymethyl-2-phenyl-thiazole-5-carboxylic acid methyl ester (5.98 g, 22.71 mmole, 1.0 eq) in CH2Cl2 (20 ml). The yellow mixture was then stirred at room temperature under nitrogen for one hour and re-cooled to 0° C. The mixture was quenched slowly by adding 2.0N NaOH dropwise, warmed to room temperature, and extracted with two portions of CH2Cl2. The organic phase was washed successively with 1.0N NaOH and brine, dried over MgSO4, and concentrated in vacuo to give a yellow oil. Silica gel chromatography eluting with (4:1) hexanes-ethyl acetate to give 6.5 g (97%) of the title compound as a yellow waxy crystalline solid. 1H NMR (CDCl3): δ 3.35 (s, 3H), 3.5 (s, 3H), 3.7 (s, 3H), 4.95 (s, 2H), 7.4-7.5 (m, 3H), 8.0 (m, 2H).

Workup

  1. temperatureto warm to RT
  2. stirringThe yellow mixture was then stirred at room temperature under nitrogen for one hour
  3. temperaturere-cooled to 0° C
  4. customThe mixture was quenched slowly
  5. additionby adding 2.0N NaOH dropwise
  6. temperaturewarmed to room temperature
  7. extractionextracted with two portions of CH2Cl2
  8. washThe organic phase was washed successively with 1.0N NaOH and brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customto give a yellow oil
  12. washSilica gel chromatography eluting with (4:1) hexanes-ethyl acetate

Sources & evidence

ORD record
ord-d7f6210751454862a3a61ffabbb809d2
Source dataset
uspto-grants-2005_08
Patent number
US06930116B2

Linked notes

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