Potassium Sodium Tartrate → N-methoxy-N-methyl-2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanamide

HRID 1881917Notes

Reaction equation

HRID 1881917 reaction equation
Cl.[CH3:2][O:3][NH:4][CH3:5].C[Al](C)C.[CH3:10][S:11][C:12]1[CH:13]=[CH:14][C:15]([CH:18]([CH2:24][CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:19]([O:21]CC)=O)=[N:16][CH:17]=1.C(=O)([O-])O.[Na+].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1>[CH3:2][O:3][N:4]([CH3:5])[C:19](=[O:21])[CH:18]([C:15]1[CH:14]=[CH:13][C:12]([S:11][CH3:10])=[CH:17][N:16]=1)[CH2:24][CH:25]1[CH2:26][CH2:27][O:28][CH2:29][CH2:30]1

Participants

7

Reactant 5

HCID 9357Potassium Sodium TartrateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 16682925TrimethylaluminumHCID 59331616ethyl 2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoate

Product 1

HCID 86641954N-methoxy-N-methyl-2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanamideYield 25%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of N-methoxymethanamine hydrochloride (1.48 g) in toluene (15 mL) was cooled to 0° C., and trimethylaluminum (1.4M hexane solution, 10.9 mL) was added dropwise. The reaction mixture was stirred at room temperature for 1.5 hr, and a solution of ethyl 2-[5-(methylsulfanyl)pyridin-2-yl]-3-(tetrahydro-2H-pyran-4-yl)propanoate (1.57 g) in toluene (15 mL) was added dropwise. The reaction mixture was stirred at room temperature for 6 hr, saturated aqueous sodium hydrogen carbonate and saturated aqueous Rochelle salt solution were added and the mixture was stirred for 1 hr. The reaction mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (404 mg, yield 25%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-hexane (9:1, volume ratio).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 6 hr
  2. stirringthe mixture was stirred for 1 hr
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0012d9126f61405886582d4329e2120b
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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