Toluene → Methyl 3-amino-5-fluorobenzoate

HRID 595993Notes

Reaction equation

HRID 595993 reaction equation
BrC1[CH:3]=[C:4]([CH:8]=[C:9]([F:11])[CH:10]=1)[C:5]([OH:7])=[O:6].[C:12]1(C)C=CC=CC=1.[Si]([CH:23]=[N+:24]=[N-])(C)(C)C>CO>[NH2:24][C:23]1[CH:3]=[C:4]([CH:8]=[C:9]([F:11])[CH:10]=1)[C:5]([O:7][CH3:12])=[O:6]

Participants

5

Reactant 3

HCID 1140TolueneHCID 167693TrimethylsilyldiazomethaneHCID 27733393-Bromo-5-fluorobenzoic acid

Product 1

HCID 3807862Methyl 3-amino-5-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-bromo-5-fluorobenzoic acid (6.12 g, 33.1 mmol) was dissolved in MeOH (10 mL) and cooled in ice-water bath and toluene (50 mL) and then TMS-diazomethane (19.84 mL, 39.7 mmol) was added dropwise. Reaction mixture was allowed to return to room temperature for 1 h and concentrated in vacuo and the residue dissolved in DCM/Ether and filtered through a short plug of silica and the filtrate evaporated in vacuo to afford the desired product which was then dissolved in MeOH (60 mL) and Pd/C 10 wt % 3.3 g was added and the mixture evacuated and stirred under 1 atm of hydrogen overnight and LCMS indicated desired product next morning. The reaction mixture was filtered through Celite and the filtrate was concnetrated in vacuo and the residue azeotroped with toluene twice and taken to the next step as such (99%). LCMS (m/z): 211.1 (MH+), 0.55 min.

Workup

  1. customReaction mixture
  2. concentrationconcentrated in vacuo
  3. dissolutionthe residue dissolved in DCM/Ether
  4. filtrationfiltered through a short plug of silica
  5. customthe filtrate evaporated in vacuo

Sources & evidence

ORD record
ord-becedcce27044c5bae184bbd4de05046
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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