Triethylamine → Methyl N-(4-fluoro-2-nitrophenyl)glycinate

HRID 656985Notes

Reaction equation

HRID 656985 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].Cl.[CH3:13][O:14][C:15](=[O:18])[CH2:16][NH2:17].C(N(CC)CC)C>C1COCC1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([NH:17][CH2:16][C:15]([O:14][CH3:13])=[O:18])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 677672,5-DifluoronitrobenzeneHCID 122755Glycine methyl ester hydrochloride2×

Product 1

HCID 10680828Methyl N-(4-fluoro-2-nitrophenyl)glycinateYield 74.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2,5-difluoronitrobenzene (54.6 g, 343 mmol), glycine methyl ester hydrochloride (47.3 g, 374 mmol) and triethylamine (114.5 mL, 818 mmol) was heated at 65° C. (internal temperature) in THF (1500 mL) over a 3 night period. Additional glycine methyl ester hydrochloride (30 g) and triethylamine (20 mL) were added and the heating continued for a further 2 nights. The mixture was cooled, filtered and evaporated to dryness. The residue was treated with 5M hydrochloric acid and the orange solid was filtered off, washed well with water (total ˜2 L) and dried under vacuum to give the product (58.5 g). The product was then extracted with ethyl acetate (600 ml total), filtered and evaporated. The residue was slurried with water (1 L), filtered and dried to give product (40 g, 51%).

Workup

  1. waitthe heating continued for a further 2 nights
  2. temperatureThe mixture was cooled
  3. filtrationfiltered
  4. customevaporated to dryness
  5. additionThe residue was treated with 5M hydrochloric acid
  6. filtrationthe orange solid was filtered off
  7. washwashed well with water (total ˜2 L)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-49fc0f7918684fa5a9b376cb9e76f981
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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