ChemicalBook CAS DataBase List 2'-Fluoro-4'-hydroxyacetophenone

2'-Fluoro-4'-hydroxyacetophenone synthesis

5synthesis methods

Product Name:2'-Fluoro-4'-hydroxyacetophenone
CAS Number:98619-07-9
Molecular formula:C8H7FO2
Molecular Weight:154.14

Preparation by reaction of acetyl chloride on 3-fluorophenol with aluminium chloride in refluxing ethylene dichloride.

701-83-7 Synthesis

701-83-7
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98619-07-9
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Yield: 80%

Reaction Conditions:

with aluminum (III) chloride;nitromethane in chloroform at 20 - 40; for 15 h;Fries Phenol Ester Rearrangement;Solvent;Temperature;

Steps:

Synthesis of 1-(2-Fluoro-4-Hydroxyphenyl)Ethanone (7).
To a solution of aluminum chloride (1.04 kg, 7.8 mol) and nitromethane (420 mL) in CHCl3 (3 L), acetate 6 (800 g, 5.2 mol) was added in portions at room temperature, and then the mixture was heated to 40 °C. After 15 h, the reaction was complete, as monitored by TLC. The reaction was cooled to room temperature and slowly poured into 1 N hydrochloric acid (8 L) containing crushed ice (1 kg). After stirring adequately, the organic layer was separated. The aqueous layer was extracted two additional times (2 L × 2). The combined organic layers were washed with water until the pH was 4-5 and were concentrated in vacuo to provide black oil. The black oil was dissolved in ethyl acetate (3.6 L) and extracted with 15% NaOH(2 L × 4). The aqueous layer was collected and adjusted to pH 5 using 6 N hydrochloric acid. The pink precipitate was filtered to provide 682 g of crude product. The crude product was dissolved in hot water (6.5 L), decolorized with active carbon (20 g), then filtered and recrystallized to give ketone 7 as a pale yellow tabular crystal (640 g, 80%). Mp 120-122 °C, (Lit.^[2] Mp 120-121 °C). ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.85 (t, J=8.4 Hz, 1H), 6.85 (s, 1H), 6.73 (dd, J=2.4 Hz, 2.0 Hz, 1H), 6.64 (dd, J=2.4 Hz, 2.0 Hz, 1H), 2.63 (d, J=5.2 Hz, 3H).

References:

Du, Fangyu;Zhou, Qifan;Shi, Yajie;Yu, Miao;Sun, Wenjiao;Chen, Guoliang [Synthetic Communications,2019,vol. 49,# 4,p. 576 - 586] Location in patent:supporting information

364-83-0 Synthesis