Methyl chloroacetate → N-[3-(Fluoromethyl)phenyl]glycine methyl ester

HRID 1493623Notes

Reaction equation

HRID 1493623 reaction equation
[F:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].C(=O)(O)[O-].[Na+].Cl[CH2:16][C:17]([O:19][CH3:20])=[O:18]>O>[CH3:20][O:19][C:17](=[O:18])[CH2:16][NH:6][C:5]1[CH:7]=[CH:8][CH:9]=[C:3]([CH2:2][F:1])[CH:4]=1

Participants

5

Reactant 3

HCID 7295Methyl chloroacetateHCID 516892Sodium BicarbonateHCID 139301133-Fluoromethyl aniline

Product 1

HCID 19829895N-[3-(Fluoromethyl)phenyl]glycine methyl esterYield 48.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

3-Fluoromethyl aniline (containing 37% 3-methylaniline, 13.6 g≡68 mmol) was mixed with dry acetonitrite (10 ml), sodium bicarbonate (15.4 g, 183 mmol) and methyl chloroacetate (12 ml, 137 mmol) and heated to 90° C. under nitrogen for 14 h. The cooled reaction mixture was poured into water (100 ml) and extracted with ethyl acetate (4×100 ml). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo to give an orange oil. The crude product was purified by chromatography on silica (Merck 9385, 1.5 kg) eluted with ether-hexane 1:4 to give Intermediate 54 (6.45 g, 48%) as a white crystalline solid, m.p. 47°-47.5°.

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate (4×100 ml)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give an orange oil
  6. customThe crude product was purified by chromatography on silica (Merck 9385, 1.5 kg)
  7. washeluted with ether-hexane 1:4

Sources & evidence

ORD record
ord-cefe145096e44c90ad9f0425c817fa04
Source dataset
uspto-grants-1991_06
Patent number
US05023255

Reaction notes

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