Formic Acid → 3-Amino-3-(4-fluoro-2-nitrophenyl)propionic acid

HRID 589377Notes

Reaction equation

HRID 589377 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.C(O)=O.[C:16]([OH:22])(=[O:21])[CH2:17]C(O)=O.C([O-])=O.[NH4+:26].Cl>O>[NH2:26][CH:6]([C:5]1[CH:8]=[CH:9][C:2]([F:1])=[CH:3][C:4]=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 762264-Fluoro-2-nitrobenzaldehydeHCID 2723923Ammonium formate

Product 1

HCID 895902893-Amino-3-(4-fluoro-2-nitrophenyl)propionic acidYield 73.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

4-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, and 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, and then stirred at 9° C. for another 4 hours. 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, and extracted with ethyl acetate (2×25 mL). The organic phase was discarded, 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 16.71 g, at a yield of 73.2%.

Workup

  1. stirringstirred at 9° 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-6f25dcfa87b74ac892e0e94e40908c81
Source dataset
uspto-grants-2016_01
Patent number
US09233098B2

Reaction notes

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