Preparation method of R-1-(naphthalene-1-yl) ethanol

A technology for ethanol and naphthoethyl ketone, which is applied in the field of preparation of R-1-ethanol, can solve the problem that the chiral purity of R-configuration alcohol needs to be further improved, and achieves the solution of metal residual risk, high recovery rate and reduction of synthesis cost. Effect

Active Publication Date: 2020-08-25
ENANTIOTECH CORP +1
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  • Description
  • Claims
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Problems solved by technology

However, this method needs to be carried out under high pressure conditions, which inevitably poses challenges for scale-up production
At the same time, as a drug, cinacalcet has a chiral purity closely related to its efficacy, and the chiral purity of the R-configuration alcohol prepared by this method (ee value is 94-98%) needs to be further improved

Method used

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  • Preparation method of R-1-(naphthalene-1-yl) ethanol
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  • Preparation method of R-1-(naphthalene-1-yl) ethanol

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preparation example Construction

[0062] Embodiments of the present invention also provide a synthetic method of R-1-(naphthalen-1-yl)ethylamine, comprising the following steps:

[0063] Synthesize R-1-(naphthalene-1-yl)ethanol according to the synthetic method described above;

[0064] The R-1-(naphthalene-1-yl)ethanol is subjected to sulfonylation and aminolysis.

[0065] R-1-(naphthalen-1-yl)ethylamine is an important intermediate of the chiral drug cinacalcet. Specifically, the reaction process of the synthetic method of above-mentioned R-1-(naphthalene-1-yl)ethylamine is as follows:

[0066]

[0067] The present invention also provides a synthetic method of cinacalcet, the steps of which include: synthesizing R-1-(naphthalen-1-yl)ethylamine by the aforementioned synthetic method.

[0068] Cinacalcet is the first drug in a new class of compounds known as calcimimetics, which activate calcium receptors in the parathyroid glands, thereby reducing the secretion of parathyroid hormone (PTH), thereby Effe...

Embodiment 1

[0073] This embodiment is a synthetic method of R-1-(naphthalene-1-yl)ethanol, the steps are as follows:

[0074] (1) Feed argon into the 5L autoclave to replace the air to form an argon atmosphere, add 100g of raw material 1-naphthyl ethyl ketone from the feed port of the autoclave, then add 1L of toluene to fully dissolve the raw material, continue Introduce argon gas for bubbling and degassing, continue bubbling for 1 hour, and degassing is completed.

[0075] (2) Under argon atmosphere, add 0.05g catalyst (wherein, the degree of polymerization of PEG n=1000) from the feed port of the autoclave, and finally add 10g potassium ethylate, after the feed is completed, quickly close the feed port.

[0076] (3) Replace the argon in the autoclave with hydrogen, then slowly feed hydrogen until the pressure in the autoclave is 3 atm, close the inflation valve; stir and react rapidly at a temperature of 40°C. During the reaction process, if the pressure drops, the hydrogen gas is sup...

Embodiment 2

[0080] This embodiment is a synthetic method of R-1-(naphthalene-1-yl)ethanol, the steps are as follows:

[0081] (1) Feed argon into the 5L autoclave to replace the air to form an argon atmosphere, add 100g of raw material 1-naphthyl ethyl ketone from the feed port of the autoclave, then add 1L of toluene to fully dissolve the raw material, continue Introduce argon gas for bubbling and degassing, continue bubbling for 1 hour, and degassing is completed.

[0082] (2) Under argon atmosphere, add 0.05g catalyst (wherein, the polymerization degree n=800 of PEG) from the feed port of the autoclave, and finally add 10g potassium ethylate, and close the feed port quickly after the feed is completed.

[0083] (3) Replace the argon in the autoclave with hydrogen, then slowly feed hydrogen until the pressure in the autoclave is 3 atm, close the inflation valve; stir and react rapidly at a temperature of 40°C. During the reaction process, if the pressure drops, the hydrogen gas is supp...

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Abstract

The invention relates to a preparation method of R-1-(naphthalene-1-yl) ethanol. The preparation method comprises the following step: carrying out asymmetric hydrogenation reaction on 1-naphthyl ethylketone under the catalysis of a catalyst; and the catalyst has structural characteristics as shown in the following formula (I). The R-1-(naphthalene-1-yl) ethanol product prepared through the preparation method is higher in chiral purity; meanwhile, the high conversion rate is guaranteed, the reaction can be carried out under the lower pressure condition, large-scale production and application are facilitated, the adopted catalyst can be recycled, heavy metal pollution is avoided, and the cost is reduced.

Description

technical field [0001] The invention relates to compound synthesis, in particular to a preparation method of R-1-(naphthalene-1-yl)ethanol. Background technique [0002] Cinacalcet, chemical name N-[(1R)-1-(1-naphthyl)ethyl]-3-(3-(trifluoromethyl)phenyl)propan-1-amine, its structure is as follows Formula (1) shown. Cinacalcet is the first drug in a new class of compounds known as calcimimetics, which activate calcium receptors in the parathyroid glands, thereby reducing the secretion of parathyroid hormone (PTH), thereby Effectively delay the progression of cardiovascular calcification, reduce the incidence of cardiovascular events, and improve all-cause mortality. At the same time, cinacalcet can also effectively reduce PTH, calcium, phosphorus, and calcium-phosphorus product in SHPT dialysis patients, reduce bone formation rate, and improve bone disease. [0003] [0004] As shown in the structural formula of formula (1), cinacalcet has a chiral center, which is gene...

Claims

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Application Information

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IPC IPC(8): C07C29/141C07C33/26C07C45/29C07C49/788
CPCC07C29/141C07C303/26C07C29/00C07C45/29C07C33/26C07C309/66C07C49/788Y02P20/584
Inventor 李彦雄蒙发明于永海黄承焕黄晋王妙红
Owner ENANTIOTECH CORP
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