Methanol → Methyl 5-bromo-2-(2-fluorophenylamino)-3,4-difluorobenzoate

HRID 929001Notes

Reaction equation

HRID 929001 reaction equation
[Br:1][C:2]1[C:3]([F:20])=[C:4]([F:19])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].O=S(Cl)Cl.[CH3:25]O>>[Br:1][C:2]1[C:3]([F:20])=[C:4]([F:19])[C:5]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:25])=[O:8]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 595193885-Bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid

Product 1

HCID 59519391Methyl 5-bromo-2-(2-fluorophenylamino)-3,4-difluorobenzoateYield 90%

Conditions

Temperature
85 °C

Procedure

To a solution of 5-bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid (13.73 g, 39.6 mmol) in MeOH (300 mL) was added SOCl2 (60 mL). After stirring at 85° C. overnight, most MeOH was removed in vacuo. The residue was neutralized with saturated sodium bicarbonate (aq.) and extracted with ethyl acetate (300 mL×3). The combined organic extract was washed with water (200 mL×3) and brine (200 mL) sequentially, dried over Na2SO4, filtered and concentrated in vacuo to afford the corresponding product (gray solid, 12.58 g, 90% yield). 1H NMR (400 MHz, CDCl3): δ 9.09 (s, 1H), 8.05 (d, 1H), 7.00-7.14 (m, 4H), 3.94 (s, 3H).

Workup

  1. custommost MeOH was removed in vacuo
  2. extractionextracted with ethyl acetate (300 mL×3)
  3. extractionThe combined organic extract
  4. washwas washed with water (200 mL×3) and brine (200 mL) sequentially
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford the corresponding product (gray solid, 12.58 g, 90% yield)

Sources & evidence

ORD record
ord-fd9dff9eacbe4002b3b6f42ed7f65dbf
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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