Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 84557435, compound

HRID 2401365Notes

Reaction equation

HRID 2401365 reaction equation
[CH3:1][C:2]1[C:3]([C:8]([O:10]C)=O)=[CH:4][S:5][C:6]=1[CH3:7].Cl.[CH3:13][NH:14][O:15][CH3:16].C([Mg]Br)(C)C>C1COCC1.CC1CCCO1>[CH3:16][O:15][N:14]([CH3:13])[C:8]([C:3]1[C:2]([CH3:1])=[C:6]([CH3:7])[S:5][CH:4]=1)=[O:10]

Participants

6

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 6397823-Thiophenecarboxylic acid, 4,5-dimethyl-, methyl esterHCID 178418365HCID 178418365, compound

Product 1

HCID 84557435HCID 84557435, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (−30° C. to −20° C.) slurry of methyl 4,5-dimethylthiophene-3-carboxylate (5.44 g, 32.0 mmol) and N,O-dimethylhydroxylamine hydrochloride (4.80 g, 49.2 mmol) in THF (45 mL) at was added slowly (over 15 min) a solution of isopropylmagnesium bromide (3.85 mL, 11.16 mmol, 2.9 M) in 2-methyl-tetrahydrofuran. After complete addition of the base, the reaction mixture was warmed to 0° C. and partitioned between 1 N HCl (55 mL) and MTBE (50 mL). The aqueous phase was extracted with MTBE (2×) and the combined organic layer was washed with water (until the pH of the aqueous was ˜5). The organic layer was dried over Na2SO4 and concentrated to give a light yellow oil. The crude product was purified on Biotage system (gradient elution 7% EtOAc:93% Hexanes to 60% EtOAc:40% Hexanes) to give the titled compound as a yellow oil (5.17 g, 25.9 mmol, 81% yield). LC/MS m/z 200 [M+H]+.

Workup

  1. additionAfter complete addition of the base
  2. custompartitioned between 1 N HCl (55 mL) and MTBE (50 mL)
  3. extractionThe aqueous phase was extracted with MTBE (2×)
  4. washthe combined organic layer was washed with water (until the pH of the
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customto give a light yellow oil
  8. customThe crude product was purified on Biotage system (gradient elution 7% EtOAc:93% Hexanes to 60% EtOAc:40% Hexanes)

Sources & evidence

ORD record
ord-8ac6979ed31c4f5781d9bc880ba45423
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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