Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 86611634, compound

HRID 521294Notes

Reaction equation

HRID 521294 reaction equation
C[Al](C)C.Cl.[CH3:6][NH:7][O:8][CH3:9].[CH2:10]([C:13]1[N:14]([CH2:26][CH2:27][CH2:28][C:29](OCC)=[O:30])[C:15]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[CH:17][C:16]=2[N:25]=1)[CH2:11][CH3:12]>C1(C)C=CC=CC=1.ClCCl>[CH3:9][O:8][N:7]([CH3:6])[C:29](=[O:30])[CH2:28][CH2:27][CH2:26][N:14]1[C:15]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[CH:17][C:16]=2[N:25]=[C:13]1[CH2:10][CH2:11][CH3:12]

Participants

6

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 16682925TrimethylaluminumHCID 57447006HCID 57447006, compound

Product 1

HCID 86611634HCID 86611634, compoundYield 98.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of trimethylaluminum in toluene (80 mL of a 2 M solution, 160 mmol) was added dropwise to a stirred suspension of N,O-dimethylhydroxylamine hydrochloride (15.6 g, 160 mmol) in dichloromethane (150 mL) at 0° C. After 15 minutes, the reaction flask was removed from bath and the solution stirred for 15 minutes at room temperature. The flask was then cooled in ice bath, and a solution of ethyl 4-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyrate (34.7 g, 107 mmol) in dichloromethane (100 mL) was added rapidly dropwise. After 15 minutes, the ice bath was removed and the solution heated at reflux to cause considerable gas evolution. After 20 hours, a 10% solution of hydrochloric acid in water (15 mL) was added slowly, followed by a saturated solution of sodium bicarbonate in water (50 mL). The layers were separated, and the aqueous mixture was extracted with dichloromethane (2×50 mL). The combined organic solutions were washed successively with a 5% solution of sodium hydroxide in water (2×50 mL) and a saturated solution of sodium bicarbonate in water (1×50 mL), dried over potassium carbonate, filtered, and concentrated under reduced pressure to provide N-methoxy-N-methyl-4-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyramide (35.9 g) as a dark oil that was used directly in the next step without further purification.

Workup

  1. customthe reaction flask was removed from bath
  2. temperatureThe flask was then cooled in ice bath
  3. waitAfter 15 minutes
  4. customthe ice bath was removed
  5. temperaturethe solution heated
  6. temperatureat reflux
  7. waitAfter 20 hours
  8. additiona 10% solution of hydrochloric acid in water (15 mL) was added slowly
  9. customThe layers were separated
  10. extractionthe aqueous mixture was extracted with dichloromethane (2×50 mL)
  11. washThe combined organic solutions were washed successively with a 5% solution of sodium hydroxide in water (2×50 mL)
  12. dry with materiala saturated solution of sodium bicarbonate in water (1×50 mL), dried over potassium carbonate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d03bdf7db2224922acc3db5253013af7
Source dataset
uspto-grants-2016_05
Patent number
US09328110B2

Reaction notes

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