Methylamine → 2-amino-4-fluoro-N-methylbenzamide

HRID 1045948Notes

Reaction equation

HRID 1045948 reaction equation
C1N=C[N:3](C(N2C=NC=C2)=O)[CH:2]=1.[NH2:13][C:14]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:15]=1[C:16](O)=[O:17].CN>C1COCC1>[NH2:13][C:14]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:15]=1[C:16]([NH:3][CH3:2])=[O:17]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 27249674-Fluoroanthranilic acid

Product 1

HCID 569516612-amino-4-fluoro-N-methylbenzamideYield 55.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Carbonyl-1,1′-diimidazole (1.26 g) was added to 2-amino-4-fluorobenzoic acid (1.0 g) in THF (16.3 mL). After stirring overnight a solution of methylamine in THF (2M, 4.9 mL) was added and the reaction stirred for 3 hours. The reaction was concentrated in vacuo and the residue dissolved in EtOAc (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The phases were separated and the organics were washed with water (2×100 mL) and then saturated aqueous brine (30 mL). The organics were dried (MgSO4, 15 g), filtered and concentrated in vacuo to give crude product (0.9 g). This material was purified by column chromatography (SiO2, 40 g, eluent 3% MeOH in DCM) to give 2-amino-4-fluoro-N-methylbenzamide (0.6 g). 1H NMR spectrum (270 MHz, DMSO): 2.69 (d, 3H), 6.28 (ddd, 1H), 6.42 (dd, 1H), 6.74 (bs, 2H), 7.48 (dd, 1H), 8.16 (q, 1H); Mass spectrum: ESI+ MH+ 169.

Workup

  1. additionwas added
  2. concentrationThe reaction was concentrated in vacuo
  3. dissolutionthe residue dissolved in EtOAc (100 mL)
  4. customThe phases were separated
  5. washthe organics were washed with water (2×100 mL)
  6. dry with materialThe organics were dried (MgSO4, 15 g)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give crude product (0.9 g)
  10. customThis material was purified by column chromatography (SiO2, 40 g, eluent 3% MeOH in DCM)

Sources & evidence

ORD record
ord-0d9806a1f4b7425f8c4409df96cb35c2
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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