Formic Acid → β-Amino-5-fluoro-2-nitrobenzenepropanoic acid

HRID 589371Notes

Reaction equation

HRID 589371 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH:7]=O.C(O)=O.[C:16]([OH:22])(=[O:21])[CH2:17]C(O)=O.C([O-])=O.[NH4+:26].Cl>O>[NH2:26][CH:7]([C:6]1[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[N+:10]([O-:12])=[O:11])[CH2:17][C:16]([OH:22])=[O:21]

Participants

7

Reactant 5

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 867Malonic AcidHCID 5870905-Fluoro-2-nitrobenzaldehydeHCID 2723923Ammonium formate

Product 1

HCID 89590308β-Amino-5-fluoro-2-nitrobenzenepropanoic acidYield 67.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

5-Fluoro-2-nitrobenzaldehyde (16.91 g, 0.10 mol), formic acid (15.2 mL, 0.40 mol) and malonic acid (13.52 g, 0.13 mol) were stirred at 45° C. for half an hour. Then ammonium formate (15.76 g, 0.25 mol) was added thereto. The reaction temperature was raised to 70° C. and stirred for 1 hour. Then it was stirred at 95° C. for another 4 hours, and then concentrated hydrochloric acid (38 mL) was added and stirred maintaining this temperature for another 1 hour. It was cooled. Water (20 mL) was added, extracted with ethyl acetate (2×25 mL), and the aqueous phase was adjusted to pH≈4.2 with 50% potassium hydroxide solution. A solid precipitated, pumping filtered, dried in vacuum to obtain a yellow solid 15.32 g, at a yield of 67.1%.

Workup

  1. stirringThen it was stirred at 95° C. for another 4 hours
  2. stirringstirred
  3. temperaturemaintaining this temperature for another 1 hour
  4. temperatureIt was cooled
  5. extractionextracted with ethyl acetate (2×25 mL)
  6. customA solid precipitated
  7. filtrationpumping filtered
  8. customdried in vacuum

Sources & evidence

ORD record
ord-497958cf160e4087935f2579cf2fe1f3
Source dataset
uspto-grants-2016_01
Patent number
US09233098B2

Reaction notes

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