Methanamine, N-methoxy-, hydrochloride (1:1) → N,2-dimethoxy-N-methyl-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetamide

HRID 2359214Notes

Reaction equation

HRID 2359214 reaction equation
[CH3:1][O:2][CH:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][N:16]([CH3:18])[N:17]=2)=[CH:9][CH:8]=1)[C:4]([OH:6])=O.C(N(CC)C(C)C)(C)C.COCCN(S(F)(F)F)CCOC.Cl.[CH3:42][NH:43][O:44][CH3:45].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:45][O:44][N:43]([CH3:42])[C:4](=[O:6])[CH:3]([O:2][CH3:1])[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][N:16]([CH3:18])[N:17]=2)=[CH:9][CH:8]=1

Participants

7

Reactant 5

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 584319992-methoxy-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetic acid

Product 1

HCID 58432087N,2-dimethoxy-N-methyl-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetamideYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methoxy-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetic acid (0.87 g, 3.5 mmol) in anhydr CH2Cl2 (10 ml) was added N,N-diisopropylethylamine (1.36 g, 10.5 mmol) while cooling over an ice bath. bis(2-Methoxyethyl)aminosulfur trifluoride (0.93 g, 4.2 mmol) was added and stirred 15 min. N,O-Dimethylhydroxylamine HCl (0.512 g, 5.25 mmol) was added and the mixture was allowed to stir overnight while warming to room temp. Saturated aqueous NaHCO3 (15 ml) was added and stirred for 5 min. The organic layer was dried over Na2SO4 and evaporated to dryness. Purification by chromatography (60% EtOAc-hexanes) gave N,2-dimethoxy-N-methyl-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetamide as a clear oil (0.425 g, 42% yield).

Workup

  1. temperaturewhile cooling over an ice bath
  2. stirringto stir overnight
  3. stirringstirred for 5 min
  4. dry with materialThe organic layer was dried over Na2SO4
  5. customevaporated to dryness
  6. customPurification by chromatography (60% EtOAc-hexanes)

Sources & evidence

ORD record
ord-9e83b48191f841cbbe5159c2066a6e3e
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

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