Potassium Carbonate → Ethyl 2-(6-acetyl-4-chloro-3-fluoro-2-iodophenoxy)propanoate

HRID 626856Notes

Reaction equation

[Cl:1][C:2]1[C:3]([F:13])=[C:4]([I:12])[C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>CN(C)C=O.O.C(OCC)(=O)C>[C:8]([C:6]1[C:5]([O:11][CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:4]([I:12])[C:3]([F:13])=[C:2]([Cl:1])[CH:7]=1)(=[O:10])[CH3:9]

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 1-(5-chloro-4-fluoro-2-hydroxy-3-iodophenyl)ethanone (5.00 g, 15.9 mmol) in N,N-dimethylformamide (80.0 mL) was treated with potassium carbonate (4.39 g, 31.8 mmol), followed by ethyl 2-bromopropanoate (2.48 mL, 19.1 mmol), and then stirred at 60° C. for 3 h. The reaction was stirred overnight at 60° C., and then worked up per the procedure below. The reaction was then re-submitted to the reaction conditions and stirred at 90° C. for 4 h. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated and washed with brine, dried over magnesium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (100% hexanes to 10% EtOAc/hexanes) gave the desired product (3.66 g, 56%) as a mixture of enantiomers. LCMS calculated for C13H14ClFIO4 (M+H)+: m/z=415.0; found: 414.9.

Workup

stirringThe reaction was stirred overnight at 60° C.
customre-submitted to the reaction conditions
stirringstirred at 90° C. for 4 h
customThe organic layer was separated
washwashed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give a crude residue
customPurification by flash column chromatography (100% hexanes to 10% EtOAc/hexanes)

Sources & evidence

ORD record: ord-6673da53b50647f48876eaafdce51dff
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309251B2

Reaction notes

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