4-Fluorobenzoic Acid → 4-Fluoro-N-methoxy-N-methylbenzamide

HRID 1498855Notes

Reaction equation

HRID 1498855 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][CH:3]=1.Cl.[CH3:12][NH:13][O:14][CH3:15].CCN=C=NCCCN(C)C.C(N(C(C)C)CC)(C)C>ClCCl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:13]([O:14][CH3:15])[CH3:12])=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 99734-Fluorobenzoic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531Diisopropylethylamine

Product 1

HCID 140693474-Fluoro-N-methoxy-N-methylbenzamideYield 57.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-fluorobenzoic acid (200 g, 1.43 mol), N,O-dimethylhydroxylamine hydrochloride (207 g, 2.14 mol) and EDCI (407 g, 2.14 mol) in dichloromethane (2 L) was added diisopropylethylamine (553 g, 4.28 mol) at 0° C. and the mixture was stirred at RT overnight. The reaction mixture was then washed with aqueous HCl (1 N, 1 L*4), water (1 L) and brine (1 L) sequentially. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give the title compound (150 g, yield 57%). MS (ES+) C9H10FNO2 requires: 183. found 184 [M+H]+; purity: 90% (UV254).

Workup

  1. washThe reaction mixture was then washed with aqueous HCl (1 N, 1 L*4), water (1 L) and brine (1 L) sequentially
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8a895d5babf9450d832bbf287c14733c
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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