Methanamine, N-methoxy-, hydrochloride (1:1) → 5-bromo-2-fluoro-N-methoxy-N-methylbenzamide

HRID 1042082Notes

Reaction equation

HRID 1042082 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].Cl.[CH3:13][NH:14][O:15][CH3:16].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>N1C=CC=CC=1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([N:14]([O:15][CH3:16])[CH3:13])=[O:8]

Participants

6

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 27363155-Bromo-2-fluorobenzoic acid

Product 1

HCID 606295205-bromo-2-fluoro-N-methoxy-N-methylbenzamideYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

A solution of compound 13 (98.0 g, 447 mmol), N,O-dimethylhydroxylamine hydrochloride (52.4 g, 537 mmol), and BOP-Cl (171 g, 671 mmol) in pyridine (490 mL) was stirred at room temperature for 3 h. After this time, the reaction mixture was diluted with water (1 L) and extracted with ethyl acetate (2×1 L). The combined extracts were washed with 1 N hydrochloric acid (3×500 mL), saturated aqueous NaHCO3 (500 mL), brine (1 L), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide 14 (106 g, 91%) as a pale yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.70-7.40 (m, 2H), 7.00 (d, J=8.8 Hz, 1H), 3.56 (br s, 3H), 3.35 (br s, 3H); ESI MS m/z 262 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate (2×1 L)
  2. washThe combined extracts were washed with 1 N hydrochloric acid (3×500 mL), saturated aqueous NaHCO3 (500 mL), brine (1 L)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4a706936d1cb41818b13e12d43338fa9
Source dataset
uspto-grants-2013_10
Patent number
US08557826B2

Reaction notes

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