Preparation method of optically pure S-configuration 1, 1-bis-(4-fluorophenyl)-2-propanol

A technology of fluorophenyl and configuration, which is applied in the field of preparation of optically pure S-configuration 1,1-bis-2-propanol, which can solve problems such as yield reduction and product racemization

Active Publication Date: 2021-02-12
SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Compared with the previous patent, although the steps of this route are one step shorter, the reagents used are almost the same, the yield is somewhat reduced, and the product is partially racemized

Method used

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  • Preparation method of optically pure S-configuration 1, 1-bis-(4-fluorophenyl)-2-propanol
  • Preparation method of optically pure S-configuration 1, 1-bis-(4-fluorophenyl)-2-propanol
  • Preparation method of optically pure S-configuration 1, 1-bis-(4-fluorophenyl)-2-propanol

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preparation example Construction

[0017] The present invention provides a method for preparing optically pure S-configuration 1,1-bis-(4-fluorophenyl)-2-propanol (II), which comprises, in an organic solvent, a compound represented by formula (I) in a catalyst and Asymmetric hydrogenation under alkaline conditions

[0018]

[0019] In some embodiments, the catalyst is a complex of a chiral ligand and a metal precursor, and the chiral ligand includes a tridentate ligand f-amphox, f-amphol, f-ampha, O-spiroPNN, Axial chiral bisphosphine ligands BINAP, SegPhos, MeO-Biphep, P-Phos, the metal precursors are ruthenium, rhodium, iridium salts, the structural formula of the chiral ligands is as follows:

[0020] In some embodiments, the molar ratio of the chiral ligand to the metal precursor is 1.0-1.5:1.

[0021] In some embodiments, the organic solvent is methanol, ethanol, isopropanol, tetrahydrofuran, toluene, 1,4-dioxane, methyl tert-butyl ether, dichloromethane, 1,2-dichloroethane Alkanes, ethyl acetate, n...

specific Embodiment approach

[0031] The reagents and raw materials used in the present invention are all available on the market.

[0032] The enantioselectivity of the present invention adopts following method to measure:

[0033] Chiracel AD-H, n-hexane / IPA=95:5, 1.0mL / min, 30℃, 230nm UV detector, t=11.72min for (S)isomer and t=13.54for (R)isomer

Embodiment 1

[0035] Add catalyst precursor [Ir(COD)Cl] to a 4.0 mL bottle under argon atmosphere 2 (6.71mg, 1.0×10 - 2 mmol, 1eq), ligand (f-amphox) (2.4×10 -2 mmol, 2.4eq) and anhydrous isopropanol ( i PrOH, 2.0 mL). The mixture was stirred at 25° C. for 12.0 h in an argon-filled glove box to obtain an orange-red solution, which can be directly used for catalytic reactions.

[0036] Add 246mg 1,1-bis-(4-fluorophenyl)-acetone (1mmol), 11.2mg potassium tert-butoxide to a glass test tube with a magnet, add 2ml of isopropanol under nitrogen protection, and add 10 μl 0.01M catalyst (S / C=10,000), filled with 4MPa hydrogen, reacted at 40°C for 24 hours. After the reaction, cool down to room temperature naturally, release the hydrogen carefully, filter with diatomaceous earth, and remove the organic solvent from the filtrate to obtain 241 mg of the product with a yield of 97% and an enantioselectivity of 80% ee.

[0037] colorless transparent liquid, 1 H NMR (400MHz, CDCl 3 )δ7.36–7.23(m,...

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Abstract

The invention discloses a preparation method of optically pure S-configuration 1, 1-bis- (4-fluorophenyl)-2-propanol. The chemical molecular structural formula of the optically pure S-configuration 1,1-bis- (4-fluorophenyl)-2-propanol is shown as (II). The S-configuration 1, 1-bis-(4-fluorophenyl)- 2-propanol is an important intermediate of a novel picolinamide bactericide, i.e., florypicoxamid,and has a very high economic value. The chemical reaction equation is shown in specification; in the reaction equation, the compound (I) is subjected to homogeneous asymmetric hydrogenation reaction,and the optically pure compound (II) is obtained with high efficiency and high selectivity. In the reaction, the catalyst is a complex of a chiral ligand and transition metal, and the complex can be prepared in advance and can also be matched in situ. The conversion number (TON, turnover number) of the catalyst is as high as 100,000 and the optical purity is as high as 97% ee. Compared with the prior art, the catalyst provided by the invention has the advantages of being high in atom economy, green, pollution-free, easy to industrialize and the like.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of optically pure S-configuration 1,1-bis-(4-fluorophenyl)-2-propanol. Background technique [0002] Florylpicoxamid (trade name: Adavelt) is a new second-generation picolinamide fungicide developed by Corteva. Its mechanism of action is the same as that of the first-generation product fenpicoxamid, and it also acts on cytochromes in the mitochondrial respiratory system of pathogenic bacteria. The Qi site of the bc1 complex, namely Qi inhibitors (QiIs), has a wider spectrum of prevention and treatment. This product is expected to be the first to be registered in the Asia-Pacific region in 2023, and its sales peak is expected to exceed US$200 million. The company plans to market the product globally for a variety of crops. According to Corteva, fenpicoxamid mainly targets grains and bananas. In addition to these markets, florylpicoxamid will become a compound...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C29/145C07C33/46C07B53/00
CPCC07B53/00C07C29/145C07B2200/07C07C33/46
Inventor 吴超马保德张绪穆
Owner SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
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