Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-3-[[(3-phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzamide

HRID 1840037Notes

Reaction equation

HRID 1840037 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:22][C:23]2[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=2)[C:26](OC)=[O:27])[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:34][NH:35][O:36][CH3:37].C([Mg]Cl)(C)C>O1CCCC1>[CH3:37][O:36][N:35]([CH3:34])[C:26](=[O:27])[C:25]1[CH:30]=[CH:31][CH:32]=[C:23]([CH2:22][N:14]([C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:9]=2)[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:18])[F:19])[CH:24]=1

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 10993963Methyl 3-(((3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino)methyl)benzoateHCID 178418918HCID 178418918, compound

Product 1

HCID 23506074N-methoxy-N-methyl-3-[[(3-phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzamideYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

To a slurry of methyl 3-[[(3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzoate (1.03 g, 0.0023 mol) and N,O-dimethyl-hydroxylamine hydrochloride (386 mg, 0.0040 mol) in 4.6 mL of tetrahydrofuran at −15° C. was added a 2.0 M solution of isopropylmagnesium chloride in THF (4.6 mL, 0.0092 mol) over 15 min. The reaction was stirred for 1 h at −15° C., then quenched with 20% aqueous ammonium chloride and extracted with ethyl acetate. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 1:1 ethyl acetate:hexane to afford 0.72 g (66%) of the desired N-methoxy-N-methyl-3-[[(3-phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzamide product as an off-white solid. HRMS calcd. for C25H25N2O4F3: 475.1845 [M+H]+, found: 475.1840.

Workup

  1. customquenched with 20% aqueous ammonium chloride
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layers were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel eluting with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-f4fa186539904014bca17c504ee99b4d
Source dataset
uspto-grants-2004_01
Patent number
US06677375B2

Reaction notes

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