Methanamine, N-methoxy-, hydrochloride (1:1) → trans-N-methoxy-N-methyl-2-phenylcyclopropane-1-carboxamide

HRID 475059

Reaction equation

HRID 475059 reaction equation
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:14][O:15][NH:16][CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:14][O:15][N:16]([CH3:17])[C:10]([C@@H:8]1[CH2:9][C@H:7]1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:12]

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 237413trans-2-Phenylcyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 15141060trans-N-methoxy-N-methyl-2-phenylcyclopropane-1-carboxamideYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of 35 (117.5 g, 724.48 mmol, 1.00 equiv) in DMF (1.2 L) under N2 was added methoxy(methyl)amine hydrochloride (82.3 g, 844.10 mmol, 1.17 equiv), HATU (329 g, 775.58 mmol, 1.07 equiv), and DIPEA (117.5 mL). The reaction mixture was stirred under N2 at 25° C. overnight and then diluted with water (700 mL). The organic phase was extracted with EtOAc (3×1 L), and the combined organic layers were washed with water (3×1 L) and brine (1×1 L), dried (Na2SO4), filtered and concentrated in vacuo. The residue purified by SiO2 chromatography and eluted with EtOAc/petroleum ether (10 to 50% EtOAc) to afford 62.5 g (42%) of trans-N-methoxy-N-methyl-2-phenylcyclopropane-1-carboxamide (37) as a light yellow oil.

Workup

  1. extractionThe organic phase was extracted with EtOAc (3×1 L)
  2. washthe combined organic layers were washed with water (3×1 L) and brine (1×1 L)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue purified by SiO2 chromatography
  7. washeluted with EtOAc/petroleum ether (10 to 50% EtOAc)

Sources & evidence

ORD record
ord-117500c628e149d69f42b203e2b8eb9b
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Linked notes

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