Methanamine, N-methoxy-, hydrochloride (1:1) → Acetamide, N-methoxy-2-[(4-methoxyphenyl)methoxy]-N-methyl-

HRID 40906Notes

Reaction equation

HRID 40906 reaction equation
[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]([CH2:7][O:8][CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.Cl.[CH3:16][NH:17][O:18][CH3:19].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH3:19][O:18][N:17]([CH3:16])[C:10](=[O:12])[CH2:9][O:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 108563932-((4-Methoxyphenyl)methoxy)acetic acid

Product 1

HCID 11424955Acetamide, N-methoxy-2-[(4-methoxyphenyl)methoxy]-N-methyl-Yield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of [(4-methoxybenzyl)oxy]acetic acid (Bioorganic and Medicinal Chemistry Letters, 2001, pp. 2837-2841) (6.86 g, 0.0350 mol) and N,O-dimethylhydroxylamine hydrochloride (3.41 g, 0.0350 mol) in DCM (100 mL) was added benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (17 g, 0.038 mol) followed by TEA (9.7 mL, 0.070 mol). The resulting mixture was stirred overnight at room temperature. The solution was then washed with water, 0.5 M HCl, saturated NaHCO3, and brine, then was dried over sodium sulfate, filtered and concentrated in vacuo. Flash column chromatography (ether/hexanes) afforded the desired product (5.75 g, 69%).

Workup

  1. washThe solution was then washed with water, 0.5 M HCl, saturated NaHCO3, and brine
  2. dry with materialwas dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c2a36b31ab0843e6ae187586f35a4131
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

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