Sulfuric Acid → 2-(4-Bromo-2,6-difluorophenyl)acetamide

HRID 1525918Notes

Reaction equation

S(=O)(=O)(O)O.[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([CH2:14][C:15]#[N:16])=[C:9]([F:17])[CH:8]=1.[OH-:18].[NH4+]>C(O)(=O)C>[Br:6][C:7]1[CH:8]=[C:9]([F:17])[C:10]([CH2:14][C:15]([NH2:16])=[O:18])=[C:11]([F:13])[CH:12]=1

Participants

Conditions

Temperature: 5 °C

Procedure

To a solution of sulfuric acid (0.96 mL, 18.1 mmol) in acetic acid (20 mL) was slowly added 2-(4-bromo-2,6-difluorophenyl)acetonitrile (0.84 g, 3.6 mmol) portion-wise while stirring, and the reaction mixture was then stirred for 1 h at 100° C. After cooling to 5° C., the mixture was carefully adjusted to pH 9 with 28-30% aq ammonium hydroxide and then was extracted with chloroform (3×40 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by flash chromatography (0-100% ethyl acetate/hexanes) provided the title product (0.71 g, 78%). MS(ES+) m/e 250 [M+H]+; 1H NMR (400 MHz, CD2Cl2) δ ppm 3.60 (s, 2 H) 5.54 (br. s., 2 H) 7.10-7.21 (m, 2 H).

Workup

stirringthe reaction mixture was then stirred for 1 h at 100° C
extractionwas extracted with chloroform (3×40 mL)
dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customPurification of the residue by flash chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-07fb6d66e8674cfdb885605441fa4bb2
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09084794B2

Reaction notes

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