KR20010025244A - Preparation of 2-Alkoxycarbonyl cyclopentanone derivatives - Google Patents
Preparation of 2-Alkoxycarbonyl cyclopentanone derivatives Download PDFInfo
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- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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Abstract
Description
본 발명은 2-알콕시카르보닐 시클로펜타논(2-Alkoxycarbonyl cyclo- pentanone) 유도체의 제조방법에 관한 것으로서 상세하게는 고순도의 2-알콕시카르보닐 시클로펜타논 유도체를 고수율로 안전하게 대량생산할 수 있는 제조방법에 관한 것이다.The present invention relates to a method for producing a 2-alkoxycarbonyl cyclopentanone derivative, and more particularly, to manufacture a high-purity 2-alkoxycarbonyl cyclopentanone derivative in high yield safely. It is about a method.
2-알콕시카르보닐 시클로펜타논 유도체는 향료, 의약품 중간체 등 여러분야에서 유용하게 사용되고 있다.2-alkoxycarbonyl cyclopentanone derivatives are usefully used in fragrances and pharmaceutical intermediates.
이러한 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법에 대해서는 여러 문헌(J. Prakt. Chem. 4th series. Vol. 9. page 43 (1959)); US Patent., 5,672,763 (1997))에 개시되어 있다. 그러나, 종래의 제조방법에 의하면, 2-알콕시카르보닐 시클로펜타논 유도체 제조시 나트륨 금속을 사용하므로 공정상 위험성을 갖고 있을 뿐만 아니라, 수율 또한 낮은 문제점이 있다. 수율이 낮은 이유는 반응시 생성되는 알코올로 인하여 반응이 가역적으로 일어나거나, 또는 이로부터 화합물 자체의 부반응이 일어나 5-알킬-시클로펜타논-2카르복실산에스테르가 생성되기 때문인 것으로 알려져 있다(J. Org. Chem. 29.2787 (1964)).For the preparation of such 2-alkoxycarbonyl cyclopentanone derivatives, see J. Prakt. Chem. 4th series. Vol. 9. page 43 (1959); US Patent. 5,672,763 (1997). However, according to the conventional manufacturing method, since sodium metal is used in the preparation of the 2-alkoxycarbonyl cyclopentanone derivative, not only has a risk in process but also a low yield. The reason for the low yield is known to be that the reaction occurs due to the alcohol produced during the reaction, or a side reaction of the compound itself results in the production of 5-alkyl-cyclopentanone-2carboxylic acid ester (J Org.Chem. 29.2787 (1964).
다른 문헌(Synthesis 1983, 996 - 997)에는 2-알콕시카르보닐 시클로펜타논 유도체의 고리화 반응시 사용되는 염기로서 포타슘 하이드리드(KH), 또는 소디움 하이드리드(NaH)를 사용하는 방법이 개시되어 있으나, 상기 방법에 사용되는 염기는 사용시 매우 주의를 요하는 위험물질이므로 대량 생산에는 매우 부적합하다.Another document (Synthesis 1983, 996-997) discloses using potassium hydride (KH), or sodium hydride (NaH) as the base used in the cyclization of 2-alkoxycarbonyl cyclopentanone derivatives. However, the base used in the method is very unsuitable for mass production because it is a dangerous substance that requires very careful use.
본 발명의 이루고자 하는 기술적 과제는 상기 문제점을 해결하여 고순도의 2-알콕시카르보닐 시클로펜타논 유도체를 고수율로 안전하게 대량생산할 수 있는 2-알콕시카르보닐 시클로펜타논(2-Alkoxycarbonyl cyclo-pentanone) 유도체의 제조방법을 제공하는데 있다.The technical problem to be solved by the present invention is to solve the above problems, 2-alkoxycarbonyl cyclopentanone (2-Alkoxycarbonyl cyclo-pentanone) derivative that can safely mass-produce high purity 2-alkoxycarbonyl cyclopentanone derivative in high yield To provide a method of manufacturing.
상기 기술적 과제를 달성하기 위하여 본 발명은 (a) 하기 화학식 2로 표시되는 아디픽산을 유기산 또는 무기산 촉매하에서 알코올과 반응시켜 하기 화학식 3으로 표시되는 아디픽산 알킬에스테르를 얻는 단계; 및In order to achieve the above technical problem, the present invention comprises the steps of (a) reacting the adipic acid represented by the formula (2) with an alcohol under an organic acid or an inorganic acid catalyst to obtain an adipic acid alkyl ester represented by the formula (3); And
상기 식에서 R은 메틸, 에틸, 이소프로필, tert-부틸 또는 벤질임.Wherein R is methyl, ethyl, isopropyl, tert-butyl or benzyl.
(b) 상기 아디픽산 알킬에스테르와 소디움 알콕시드 또는 포타슘 알콕시드를 용매하에서 반응시켜 하기 화학식 1로 표시되는 2-알콕시카르보닐 시클로펜타논 유도체를 얻는 단계;(b) reacting the adipic acid alkyl ester with sodium alkoxide or potassium alkoxide in a solvent to obtain a 2-alkoxycarbonyl cyclopentanone derivative represented by Formula 1 below;
화학식 1Formula 1
상기 식에서 R은 메틸, 에틸, 이소프로필, tert-부틸 또는 벤질임.Wherein R is methyl, ethyl, isopropyl, tert-butyl or benzyl.
를 포함하는 것을 특징으로 하는 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법을 제공한다.It provides a method for producing a 2-alkoxycarbonyl cyclopentanone derivative comprising a.
본 발명에 따른 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법에 있어서, 상기 (a)단계의 알코올로는 메탄올, 에탄올, 이소프로판올, tert-부탄올, 벤질 알코올 등이 사용될 수 있고, 유기산 또는 무기산 촉매로는 황산이나 p-톨루엔설폰산 등이 사용될 수 있다.In the method for producing a 2-alkoxycarbonyl cyclopentanone derivative according to the present invention, the alcohol of step (a) may be methanol, ethanol, isopropanol, tert-butanol, benzyl alcohol, etc. As the sulfuric acid or p-toluenesulfonic acid may be used.
또한, 본 발명에 따른 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법에 있어서, 상기 (b)단계의 용매로는 톨루엔, 벤젠 또는 크실렌 등이 사용될 수 있다.In addition, in the preparation method of the 2-alkoxycarbonyl cyclopentanone derivative according to the present invention, toluene, benzene or xylene may be used as the solvent of step (b).
이하, 본 발명의 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법에 대하여 상세히 설명하기로 한다.Hereinafter, a method for preparing the 2-alkoxycarbonyl cyclopentanone derivative of the present invention will be described in detail.
본 발명의 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법을 하기 반응식 1에 나타냈다.The preparation method of the 2-alkoxycarbonyl cyclopentanone derivative of the present invention is shown in Scheme 1 below.
상기 식에서 R은 메틸, 에틸, 이소프로필, tert-부틸 또는 벤질임.Wherein R is methyl, ethyl, isopropyl, tert-butyl or benzyl.
상기 반응식 1에 나타낸 바와 같이, 본 발명의 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법은 먼저 아디픽산을 유기산 또는 무기산 촉매하에서 알코올과 반응시켜 아디픽산 알킬에스테르를 얻는 단계를 포함한다.As shown in Scheme 1, the method for preparing the 2-alkoxycarbonyl cyclopentanone derivative of the present invention includes first reacting adipic acid with an alcohol under an organic or inorganic acid catalyst to obtain an adipic acid alkyl ester.
아디픽산 알킬에스테르를 얻는 종래의 방법으로는 아디픽산을 알코올 용매하에서 티오닐클로리드(SOCl2)를 이용하는 방법(Brian S. Furniss at el., "Vogel's Textbook of Practical Organic Chemistry", 5th Ed., 1989, page 695 - 707)이 개시되어 있으나, 이 방법은 대량 생산시 과량의 유독가스의 배출로 인한 환경 공해를 일으킬 뿐만 아니라 제조 공정 시간이 길다. 따라서 본 발명에 따르면, 아디픽산을 황산이나 p-톨루엔설폰산과 같은 유기산 또는 무기산 촉매하에서 메탄올, 에탄올, 이소프로판올, tert-부탄올, 벤질 알코올 등과 같은 알코올 용매와 반응시키므로써 환경 공해 문제를 발생시키지 않으면서 비교적 짧은 시간내에 아디픽산 알킬에스테르를 제조할 수 있다.Conventional methods for obtaining adipic acid alkyl esters include adipic acid using thionyl chloride (SOCl 2 ) in an alcohol solvent (Brian S. Furniss at el., "Vogel's Textbook of Practical Organic Chemistry", 5th Ed., 1989, page 695-707), but this method not only causes environmental pollution due to the release of excess toxic gases in mass production, but also has a long manufacturing process time. Therefore, according to the present invention, adipic acid is reacted with an alcohol solvent such as methanol, ethanol, isopropanol, tert-butanol, benzyl alcohol, etc. under an organic or inorganic acid catalyst such as sulfuric acid or p-toluenesulfonic acid without causing environmental pollution problems. Adipic acid alkyl esters can be prepared in a relatively short time.
본 발명에 따른 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법에 있어서, 아디픽산 알킬에스테르를 제조하는 방법을 예를 들어 자세히 살펴보면 다음과 같다.In the preparation method of the 2-alkoxycarbonyl cyclopentanone derivative according to the present invention, a method of preparing adipic acid alkyl ester is described in detail as follows.
먼저, 아디픽산을 10 내지 20 배 부피 비의 알코올 용매 하에서 황산 등의 유기산과 p-톨루엔설폰산(p-TsOH) 등과 같은 무기산을 0.5 내지 10% 무게비의 촉매량 사용하여 3 내지 5 시간 동안 가열 환류한후, 알코올 용매를 농축하여 제거하고, 5 내지 10 mmHg의 감압 하에서 130 내지 200℃의 온도 범위에서 증류하여 아디픽산 알킬에스테르를 얻는다. 이 때, 바람직하게는 아디픽산을 10배 부피비의 알코올 용매하에서 5% 무게비의 황산(H2SO4) 또는 p-톨루엔설폰산(p-TsOH)을 사용하여 4시간 동안 가열 환류한 후 5 내지 10 mmHg의 감압 하에서 130 내지 200℃의 온도 범위에서 증류한다.First, adipic acid was heated to reflux for 3 to 5 hours using a catalytic amount of 0.5 to 10% by weight of an organic acid such as sulfuric acid and an inorganic acid such as p-toluenesulfonic acid (p-TsOH) under an alcohol solvent in a 10 to 20 times volume ratio. After that, the alcohol solvent is removed by concentration, and distilled at a temperature range of 130 to 200 ° C. under a reduced pressure of 5 to 10 mmHg to obtain an adipic acid alkyl ester. At this time, preferably, the adipic acid is heated to reflux for 4 hours using sulfuric acid (H 2 SO 4 ) or p-toluenesulfonic acid (p-TsOH) in a 5% weight ratio in an alcohol solvent in a 10-fold volume ratio, and then 5 to 5 to. Distillation is carried out in a temperature range of 130 to 200 ° C. under a reduced pressure of 10 mmHg.
또한, 상기 반응식 1에 나타낸 바와 같이, 본 발명의 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법은 전술한 방법에 의해 얻어진 아디픽산 알킬에스테르와 소디움 알콕시드 또는 포타슘 알콕시드를 톨루엔, 벤젠 또는 크실렌과 같은 용매하에서 반응시켜 2-알콕시카르보닐 시클로펜타논 유도체를 얻는 단계를 포함한다.In addition, as shown in Scheme 1, the method for producing the 2-alkoxycarbonyl cyclopentanone derivative of the present invention is obtained by using the adipic acid alkyl ester and sodium alkoxide or potassium alkoxide obtained by the above-described method in toluene, benzene or xylene. Reacting in a solvent such as to obtain a 2-alkoxycarbonyl cyclopentanone derivative.
본 발명에 따른 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법은 염기로서 화학적으로 안정한 소디움 알콕시드 또는 포타슘 알콕시드를 사용하여 디이크만 고리화 반응(Dieckmann Cyclization)을 진행하므로써 공정에 따른 위험성 없이 안전하게 고순도의 2-알콕시카르보닐 시클로펜타논 유도체를 고수율로 대량생산 할 수 있다.The preparation method of the 2-alkoxycarbonyl cyclopentanone derivative according to the present invention is based on the Dieckmann Cyclization using a chemically stable sodium alkoxide or potassium alkoxide as a base, without the risks associated with the process. It is possible to safely mass-produce high purity 2-alkoxycarbonyl cyclopentanone derivatives in high yield.
본 발명에 따른 2-알콕시카르보닐 시클로펜타논 유도체의 제조방법에 있어서, 아디픽산 알킬에스테르로부터 2-알콕시카르보닐 시클로펜타논 유도체를 제조하는 방법을 예를 들어 자세히 살펴보면 다음과 같다.In the preparation method of the 2-alkoxycarbonyl cyclopentanone derivative according to the present invention, a method of preparing the 2-alkoxycarbonyl cyclopentanone derivative from an adipic acid alkyl ester will be described in detail as follows.
아디픽산 알킬에스테르를 벤젠, 톨루엔, 크실렌 등의 용매하에서 1 내지 2 당량의 소디움메톡시드 또는 소디움에톡시드와 같은 소디움알콕시드 또는 포타슘 tert-부톡시드와 같은 포타슘 알콕시드를 사용하여 70 내지 90℃에서 2 내지 5 시간 동안 반응한 후, 반응에서 생성된 알코올(메탄올, 에탄올 또는 tert-부탄올)을 상압 또는 예를 들어 5 내지 10 mmHg의 감압 하에서 제거한다.The adipic acid alkyl ester is 70-90 ° C. using sodium alkoxide such as sodium methoxide or sodium ethoxide or potassium alkoxide such as potassium tert-butoxide in a solvent such as benzene, toluene, xylene or the like. After reacting for 2 to 5 hours at, the alcohol (methanol, ethanol or tert-butanol) produced in the reaction is removed under atmospheric pressure or under reduced pressure of, for example, 5 to 10 mmHg.
이어서, 반응혼합물을 0℃ 내지 5℃로 냉각하고, 10% 내지 20% 가성소다수를 3 내지 5배의 부피비를 가하여 염기성화(pH 9∼12) 시킨 후 미반응된 화학식 화합물(Ⅲ)을 제거하고, 수용액 층을 10 내지 20%의 염산 또는 초산 수용액을 4 내지 6배의 부피 비를 사용하여 산성화(pH 6∼6.5) 하고 2 내지 6배 부피 비의 톨루엔 또는 벤젠 등으로 추출한 후 5 내지 7% 탄산나트륨(Na2CO3) 수용액으로 3 내지 5 mmHg 의 감압 하에서 80℃ 내지 120℃의 범위에서 감압증류하여 2-알콕시카르보닐 시클로펜타논을 얻는다. 이 때, 아디픽산 에스테르를 톨루엔 용매하에서 1.5 당량의 소디움알콕시드(소디움메톡시드(NaOMe) 또는 소디움에톡시드(NaOEt)를 사용하여 90℃에서 3시간 반응 후 10 mmHg의 감압 하에서 반응에서 생성된 알코올을 제거한 후 반응 혼합물을 10℃로 냉각하고, 10% 가성소다수를 3배의 부피비를 가하여 염기화(pH≒11)시킨 후 미반응된 화학식 (III)의 화합물을 제거한 후 수용액을 10%의 초산 수용액을 4.5배 부피 비로 사용하여 산성화(pH 6.5)하고, 6배 부피 비의 톨루엔으로 추출한 후 7% 탄산나트륨(Na2CO3) 수용액으로 세척하여, 3 mmHg의 감압 하에서 80 내지 120℃의 범위에서 감압증류하여 2-알콕시카르보닐 시클로펜타논을 얻는 것이 바람직하다.Subsequently, the reaction mixture was cooled to 0 ° C to 5 ° C, 10% to 20% of caustic soda water was basified (pH 9-12) by adding a volume ratio of 3 to 5 times to remove unreacted formula compound (III). The aqueous layer was acidified (pH 6-6.5) with 10-20% hydrochloric acid or acetic acid aqueous solution using 4-6 times volume ratio, extracted with 2-6 times volume ratio of toluene or benzene and then 5-7. Distillation under reduced pressure with an aqueous solution of% sodium carbonate (Na 2 CO 3 ) under reduced pressure of 3 to 5 mmHg in the range of 80 to 120 ° C. to obtain 2-alkoxycarbonyl cyclopentanone. At this time, the adipic acid ester was reacted with 1.5 equivalents of sodium alkoxide (sodium methoxide (NaOMe) or sodium ethoxide (NaOEt) in a toluene solvent at 90 DEG C for 3 hours, and then produced in the reaction under reduced pressure of 10 mmHg. After the alcohol was removed, the reaction mixture was cooled to 10 ° C., and 10% caustic soda water was basified (pH ≒ 11) by adding 3 times the volume ratio, and after removing the unreacted compound of formula (III), an aqueous solution of 10% It was acidified (pH 6.5) using an aqueous solution of acetic acid at 4.5 times by volume, extracted with 6 times by volume of toluene and washed with 7% aqueous solution of sodium carbonate (Na 2 CO 3 ), in the range of 80 to 120 ° C. under reduced pressure of 3 mmHg. It is preferable to distillate under reduced pressure in order to obtain 2-alkoxycarbonyl cyclopentanone.
이하, 본 발명을 실시예를 통해 더욱 상세히 설명하고자 하는데, 본 발명의 범위가 하기 실시예로 한정되는 것이 아님은 물론이다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited to the following Examples.
실시예 1 : 2-메톡시카르보닐 시클로펜타논(2-Methoxycarbonyl cyclo-pentanone)의 제조Example 1 Preparation of 2-Methoxycarbonyl cyclo-pentanone
제1단계 : 아디픽산 디메틸에스테르(Methyl Adipate or Adipic acid dimethylester)의 제조First Step: Preparation of Adipic Acid or Dipic Acid Dimethyl Ester
아디픽산(Adipic acid) 1.5 kg(10.27mole)을 메탄올 12L에 녹이고, p-톨루엔설폰산(p-TsOH) 50g을 가한 후 3시간 동안 가열 환류하였다. 얻어진 반응 혼합물을 상온으로 냉각한 후 감압농축하여 메탄올을 제거하고, 잉여물에 물 5L를 가한 후 디클로로메탄 5kg으로 2회 추출하고, 유기층을 무수망초(MgSO4)로 건조 후 감압농축하였다. 이어서, 얻어진 crude 생성물을 10 mmHg의 감압하에서 증류하여 맑은 액체의 상기 표제 화합물 1.79kg(수율:98%)을 얻었다. 얻어진 표제 화합물의 분석 결과는 다음과 같다.1.5 kg (10.27 mole) of adipic acid was dissolved in 12 L of methanol, and 50 g of p-toluenesulfonic acid (p-TsOH) was added thereto, followed by heating to reflux for 3 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure to remove methanol, 5L of water was added to the excess, extracted twice with 5 kg of dichloromethane, and the organic layer was dried over anhydrous manganese (MgSO 4 ) and concentrated under reduced pressure. The crude product obtained was then distilled off under reduced pressure of 10 mmHg to give 1.79 kg (yield: 98%) of the title compound as a clear liquid. The analysis results of the obtained title compound are as follows.
bp: 137∼139℃/10 mmHgbp: 137-139 ° C / 10 mmHg
원소분석:Elemental Analysis:
기준치: C8H14O4C; 55.16, H; 8.10Baseline: C 8 H 14 O 4 C; 55.16, H; 8.10
실측치: C8H14O4C; 55.16, H; 8.11Found: C 8 H 14 O 4 C; 55.16, H; 8.11
NMR(CDCl3) δ 1.25 (m, 4H), 2.54 (dt, 4H), 3.57 (s, 6H)NMR (CDCl 3 ) δ 1.25 (m, 4H), 2.54 (dt, 4H), 3.57 (s, 6H)
GC ConditionGC Condition
Column: CBP 20, 25 inch, 0.25 capillary columnColumn: CBP 20, 25 inch, 0.25 capillary column
Temp: 60℃ → 230℃, rate : 15℃/minTemp: 60 ℃ → 230 ℃, rate: 15 ℃ / min
Ret. Time: 10.91Ret. Time: 10.91
purity: 99.8%purity: 99.8%
제2단계 : 2-메톡시카르보닐 시클로펜타논(2-Methoxycarbonyl cyclo- pentanone의 제조Second Step: Preparation of 2-Methoxycarbonyl Cyclopentanone
상기 얻어진 아디픽산 디메틸에스테르 1.0 kg(5.74 mole)을 톨루엔 5.0 kg에 넣고, 교반하면서 30℃에서 소디움메톡시드 0.5 kg(9.26 mole)을 투입하여 90℃에서 3시간 동안 교반하였다. 동일온도에서 감압 증류하여 톨루엔과 생성된 알코올 1 kg 정도를 제거하고, 5℃로 냉각 후 10% 가성소다수 15 kg를 투입하였다. 이어서, 층 분리를 하여 톨루엔 층을 제거하고, 수용액 층을 5℃로 냉각 후 10% 초산 수용액을 가하여 pH를 6.5 내지 7.0으로 조절한 후, 톨루엔 5kg로 3회 추출하였다. 톨루엔 층을 7% 탄산나트륨 수용액 2 kg로 세척하고, 감압 하에서 85∼110℃의 범위에서 증류하여 맑은 액체상의 상기 표제 화합물 695 g(수율:85%)을 얻었다. 얻어진 표제 화합물의 분석 결과는 다음과 같다.1.0 kg (5.74 mole) of the adipic acid dimethyl ester obtained above was added to 5.0 kg of toluene, 0.5 kg (9.26 mole) of sodium methoxide was added at 30 ° C. with stirring, and stirred at 90 ° C. for 3 hours. Distillation under reduced pressure at the same temperature to remove about 1 kg of toluene and alcohol produced, and after cooling to 5 ℃ 15 kg of 10% caustic soda water. Subsequently, the layers were separated to remove the toluene layer, the aqueous layer was cooled to 5 ° C., and then the pH was adjusted to 6.5 to 7.0 by adding 10% acetic acid aqueous solution, followed by extraction three times with 5 kg of toluene. The toluene layer was washed with 2 kg of 7% aqueous sodium carbonate solution and distilled under reduced pressure in the range of 85 to 110 ° C. to give 695 g (yield: 85%) of the title compound as a clear liquid. The analysis results of the obtained title compound are as follows.
bp 85∼110℃/10 mmHgbp 85 to 110 ° C / 10 mmHg
원소분석:Elemental Analysis:
기준치: C7H10O3C; 59.14, H; 7.09Baseline: C 7 H 10 O 3 C; 59.14, H; 7.09
실측치: C7H10O3C; 59.22, H; 7.10Found: C 7 H 10 O 3 C; 59.22, H; 7.10
NMR(CDCl3) δ 1.99 (m, 4H), 2.20 (m, 2H), 2.76 (t, 1H), 3.56 (s, 3H)NMR (CDCl 3 ) δ 1.99 (m, 4H), 2.20 (m, 2H), 2.76 (t, 1H), 3.56 (s, 3H)
GC ConditionGC Condition
Column: CBP 20, 25 inch, 0.25 capillary columnColumn: CBP 20, 25 inch, 0.25 capillary column
Temp: 60℃ → 230℃, rate : 15℃/minTemp: 60 ℃ → 230 ℃, rate: 15 ℃ / min
Ret. Time: 9.65Ret. Time: 9.65
purity: 99.5%purity: 99.5%
실시예 2 : 2-에톡시카르보닐 시클로펜타논(2-Ethoxycarbonyl cyclo- pentanone)의 제조Example 2 Preparation of 2-Ethoxycarbonyl Cyclopentanone
제1단계 : 아디픽산 디에틸에스테르(Ethyl Adipate or Adipic acid dimethylester)의 제조Step 1: Preparation of Dithyl Diethyl Ester (Ethyl Adipate or Adipic Acid Dimethyl Ester)
에탄올 10 L를 사용하여 실시예 1의 제1단계와 동일한 방법으로 제조하여 상기 표제 화합물 2.01 kg(수율:97%)을 얻었다. 얻어진 표제 화합물의 분석 결과는 다음과 같다.It was prepared in the same manner as in the first step of Example 1 using 10 L of ethanol to obtain 2.01 kg (yield: 97%) of the title compound. The analysis results of the obtained title compound are as follows.
bp: 140∼144℃/10 mmHgbp: 140 to 144 ° C / 10 mmHg
원소분석:Elemental Analysis:
기준치: C10H18O4C; 59.39, H; 8.97Baseline: C 10 H 18 O 4 C; 59.39, H; 8.97
실측치: C10H18O4C; 60.05, H; 9.00Found: C 10 H 18 O 4 C; 60.05, H; 9.00
NMR(CDCl3) δ 1.22 (t, 6H), 1.27 (m, 4H), 2.59 (dt, 4H), 4.12 (q, 4H)NMR (CDCl 3 ) δ 1.22 (t, 6H), 1.27 (m, 4H), 2.59 (dt, 4H), 4.12 (q, 4H)
GC ConditionGC Condition
Column: CBP 20, 25 inch, 0.25 capillary columnColumn: CBP 20, 25 inch, 0.25 capillary column
Temp: 60℃ → 230℃, rate : 15℃/minTemp: 60 ℃ → 230 ℃, rate: 15 ℃ / min
Ret. Time: 12.41Ret. Time: 12.41
purity: 99.6%purity: 99.6%
제2단계 : 2-에톡시카르보닐 시클로펜타논 (2-Ethoxycarbonyl cyclo- pentanone)의 제조Second Step: Preparation of 2-Ethoxycarbonyl Cyclopentanone
상기 얻어진 아디픽산 디에틸에스테르 1.16 kg(5.74 mole)과 소디움에톡시드 630 g(9.26 mole)을 사용하여 상기 실시예 2의 제2단계와 동일한 방법으로 제조하여 맑은 액체상의 상기 목적 화합물 767g(수율:85%)을 얻었다. 얻어진 표제 화합물의 분석 결과는 다음과 같다.Using the obtained adipic acid diethyl ester 1.16 kg (5.74 mole) and sodium ethoxide 630 g (9.26 mole) was prepared in the same manner as in the second step of Example 2 to give 767 g of the target compound as a clear liquid (yield) : 85%). The analysis results of the obtained title compound are as follows.
bp: 85∼120℃/10 mmHgbp: 85-120 degreeC / 10 mmHg
원소분석:Elemental Analysis:
기준치: C8H12O3C; 61.52, H; 7.74Baseline: C 8 H 12 O 3 C; 61.52, H; 7.74
실측치: C8H12O3C; 61.55, H; 7.79Found: C 8 H 12 O 3 C; 61.55, H; 7.79
NMR(CDCl3) δ 1.11 (t, 3H), 1.95 (m, 4H), 2.24 (m, 2H), 2.81 (t, 1H), 4.22 (q, 2H)NMR (CDCl 3 ) δ 1.11 (t, 3H), 1.95 (m, 4H), 2.24 (m, 2H), 2.81 (t, 1H), 4.22 (q, 2H)
GC ConditionGC Condition
Column: CBP 20, 25 inch, 0.25 capillary columnColumn: CBP 20, 25 inch, 0.25 capillary column
Temp: 60℃ → 230℃, rate : 15℃/minTemp: 60 ℃ → 230 ℃, rate: 15 ℃ / min
Ret. Time: 11.00Ret. Time: 11.00
purity: 99.6%purity: 99.6%
실시예 3 : 2-tert-부톡시카르보닐 시클로펜타논(2-tert-butoxycarbonyl cyclopentanone)의 제조Example 3 Preparation of 2-tert-butoxycarbonyl cyclopentanone
제1단계 : 아디픽산 tert-부틸에스테르(tert-Butyl Adipate or Adipic acid di-tert-butylester)의 제조Step 1: Preparation of tert-Butyl Adipate or Adipic acid di-tert-butylester
tert-부틸알콜 8L를 사용하여 실시예 1의 제1단계와 동일한 방법으로 제조하여 상기 표제 화합물 2.34 kg(수율:93%)을 얻었다. 얻어진 표제 화합물의 분석 결과는 다음과 같다.8 L of tert-butyl alcohol was prepared in the same manner as in the first step of Example 1 to obtain 2.34 kg (yield: 93%) of the title compound. The analysis results of the obtained title compound are as follows.
bp: 130∼145℃/5 mmHgbp: 130 to 145 ° C / 5 mmHg
원소분석:Elemental Analysis:
기준치: C14H26O4C; 65.09, H; 10.14Baseline: C 14 H 26 O 4 C; 65.09, H; 10.14
실측치: C14H26O4C; 65.10, H; 10.15Found: C 14 H 26 O 4 C; 65.10, H; 10.15
NMR(CDCl3) δ 0.98 (s, 18H), 1.29 (m, 4H), 2.58 (dt, 4H)NMR (CDCl 3 ) δ 0.98 (s, 18H), 1.29 (m, 4H), 2.58 (dt, 4H)
GC ConditionGC Condition
Column: CBP 20, 25 inch, 0.25 capillary columnColumn: CBP 20, 25 inch, 0.25 capillary column
Temp: 60℃ → 250℃, rate : 15℃/minTemp: 60 ℃ → 250 ℃, rate: 15 ℃ / min
Ret. Time: 17.80Ret. Time: 17.80
purity: 99.2%purity: 99.2%
제2단계 : 2-tert-부톡시카르보닐 시클로펜타논(2-tert-butoxycarbonyl cyclopentanone)의 제조Second Step: Preparation of 2-tert-butoxycarbonyl cyclopentanone
아디픽산 디-tert-부틸에스테르 1.48 kg(5.74 mole)과 포타시움-tert-부톡시드 826g(8.61 mole)을 사용하여 상기 실시예 1의 제2단계와 동일한 방법으로 제조하여 맑은 액체상의 상기 표제 화합물 844g(수율:80%)을 얻었다. 얻어진 표제 화합물의 분석 결과는 다음과 같다.844 g of the title compound as a clear liquid, prepared in the same manner as in the second step of Example 1, using 1.48 kg (5.74 mole) of adipic acid di-tert-butyl ester and 826 g (8.61 mole) of potassium-tert-butoxide. (Yield: 80%) was obtained. The analysis results of the obtained title compound are as follows.
bp: 89∼118℃/5 mmHgbp: 89-118 degreeC / 5 mmHg
원소분석:Elemental Analysis:
기준치: C8H12O3C; 61.52, H; 7.74Baseline: C 8 H 12 O 3 C; 61.52, H; 7.74
실측치: C8H12O3C; 61.55, H; 7.79Found: C 8 H 12 O 3 C; 61.55, H; 7.79
NMR(CDCl3) δ 0.96 (s, 9H), 1.85 (m, 4H), 2.25 (m, 2H), 2.79 (t, 1H)NMR (CDCl 3 ) δ 0.96 (s, 9H), 1.85 (m, 4H), 2.25 (m, 2H), 2.79 (t, 1H)
GC ConditionGC Condition
Column: CBP 20, 25 inch, 0.25 capillary columnColumn: CBP 20, 25 inch, 0.25 capillary column
Temp: 60℃ → 230℃, rate : 15℃/minTemp: 60 ℃ → 230 ℃, rate: 15 ℃ / min
Ret. Time: 14.5Ret. Time: 14.5
purity: 99.6%purity: 99.6%
전술한 내용은 본 발명의 최적의 실시예들을 개시한 것이다. 여기서 특정한 용어들이 사용되었으나, 이는 단지 본 발명의 설명을 보다 쉽고 명확하게 표현하기 위한 목적에서 한정적으로 사용된 것에 불과하며 특허청구범위에 기재된 본 발명의 범위를 제한하기 위해 사용된 것은 아니다.The foregoing discloses optimal embodiments of the present invention. Although specific terms have been used herein, these are only used for the purpose of expressing the description of the present invention more easily and clearly, and are not used to limit the scope of the present invention described in the claims.
본 발명의 제조방법에 따르면, 고순도의 2-알콕시카르보닐 시클로펜타논 유도체를 고수율로 안전하게 대량생산할 수 있다.According to the production method of the present invention, high-purity 2-alkoxycarbonyl cyclopentanone derivatives can be safely mass-produced in high yield.
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| US5600013A (en) * | 1993-05-28 | 1997-02-04 | Rhone-Poulenc Chimie | Preparation of cyclic ketones |
| US5672763A (en) * | 1995-06-28 | 1997-09-30 | Bayer Aktiengesellschaft | Process for the preparation of 2-substituted cyclopentanones |
| US5856581A (en) * | 1993-05-28 | 1999-01-05 | Rhone-Poulenc Chimie | Preparation of cyclic ketones |
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|---|---|---|---|---|
| US4895985A (en) * | 1987-09-09 | 1990-01-23 | Basf Aktiengesellschaft | Preparation of cyclopentanone |
| US5600013A (en) * | 1993-05-28 | 1997-02-04 | Rhone-Poulenc Chimie | Preparation of cyclic ketones |
| US5856581A (en) * | 1993-05-28 | 1999-01-05 | Rhone-Poulenc Chimie | Preparation of cyclic ketones |
| US5672763A (en) * | 1995-06-28 | 1997-09-30 | Bayer Aktiengesellschaft | Process for the preparation of 2-substituted cyclopentanones |
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