CN105481694B - 一种4‑甲氧基乙酰乙酸乙酯的合成方法 - Google Patents
一种4‑甲氧基乙酰乙酸乙酯的合成方法 Download PDFInfo
- Publication number
- CN105481694B CN105481694B CN201510877720.0A CN201510877720A CN105481694B CN 105481694 B CN105481694 B CN 105481694B CN 201510877720 A CN201510877720 A CN 201510877720A CN 105481694 B CN105481694 B CN 105481694B
- Authority
- CN
- China
- Prior art keywords
- added
- reaction system
- temperature
- reaction
- suction filtration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000010189 synthetic method Methods 0.000 title claims abstract description 8
- -1 methoxyl group Chemical group 0.000 title abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 116
- 239000007787 solid Substances 0.000 claims abstract description 77
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000000967 suction filtration Methods 0.000 claims abstract description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 28
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000012312 sodium hydride Substances 0.000 claims abstract description 23
- 229910000104 sodium hydride Inorganic materials 0.000 claims abstract description 23
- 239000000706 filtrate Substances 0.000 claims abstract description 21
- 239000012074 organic phase Substances 0.000 claims abstract description 21
- 150000002148 esters Chemical class 0.000 claims abstract description 16
- 238000001514 detection method Methods 0.000 claims abstract description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- 239000012044 organic layer Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims description 34
- 239000007788 liquid Substances 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000013019 agitation Methods 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 10
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000012535 impurity Substances 0.000 abstract description 4
- 238000004061 bleaching Methods 0.000 abstract description 2
- 239000007844 bleaching agent Substances 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 230000009467 reduction Effects 0.000 abstract description 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 abstract 1
- 238000010792 warming Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 48
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 239000012065 filter cake Substances 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 15
- 239000002480 mineral oil Substances 0.000 description 14
- 235000010446 mineral oil Nutrition 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 150000002240 furans Chemical class 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 239000011259 mixed solution Substances 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000007689 inspection Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010931 ester hydrolysis Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 229940124321 AIDS medicine Drugs 0.000 description 1
- 229940099797 HIV integrase inhibitor Drugs 0.000 description 1
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- RHWKPHLQXYSBKR-BMIGLBTASA-N dolutegravir Chemical compound C([C@@H]1OCC[C@H](N1C(=O)C1=C(O)C2=O)C)N1C=C2C(=O)NCC1=CC=C(F)C=C1F RHWKPHLQXYSBKR-BMIGLBTASA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003084 hiv integrase inhibitor Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002850 integrase inhibitor Substances 0.000 description 1
- 229940124524 integrase inhibitor Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940014075 tivicay Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cosmetics (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
Claims (4)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510877720.0A CN105481694B (zh) | 2015-12-04 | 2015-12-04 | 一种4‑甲氧基乙酰乙酸乙酯的合成方法 |
CN201710490010.1A CN107311861B (zh) | 2015-12-04 | 2015-12-04 | 一种4-甲氧基乙酰乙酸乙酯及其合成方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510877720.0A CN105481694B (zh) | 2015-12-04 | 2015-12-04 | 一种4‑甲氧基乙酰乙酸乙酯的合成方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710490010.1A Division CN107311861B (zh) | 2015-12-04 | 2015-12-04 | 一种4-甲氧基乙酰乙酸乙酯及其合成方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105481694A CN105481694A (zh) | 2016-04-13 |
CN105481694B true CN105481694B (zh) | 2017-08-25 |
Family
ID=55669016
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710490010.1A Active CN107311861B (zh) | 2015-12-04 | 2015-12-04 | 一种4-甲氧基乙酰乙酸乙酯及其合成方法 |
CN201510877720.0A Expired - Fee Related CN105481694B (zh) | 2015-12-04 | 2015-12-04 | 一种4‑甲氧基乙酰乙酸乙酯的合成方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710490010.1A Active CN107311861B (zh) | 2015-12-04 | 2015-12-04 | 一种4-甲氧基乙酰乙酸乙酯及其合成方法 |
Country Status (1)
Country | Link |
---|---|
CN (2) | CN107311861B (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111533656A (zh) * | 2020-05-27 | 2020-08-14 | 龙曦宁(上海)医药科技有限公司 | 一种4-甲氧基-3-氧代丁酸叔丁酯的合成方法 |
CN113831242A (zh) * | 2021-10-11 | 2021-12-24 | 瑞孚信江苏药业股份有限公司 | 一种4-甲氧基乙酰乙酸甲酯的制备方法 |
CN114349635B (zh) * | 2021-12-31 | 2023-09-01 | 瑞孚信江苏药业股份有限公司 | 一种度鲁特韦核心中间体的合成方法 |
CN114213249B (zh) * | 2021-12-31 | 2023-09-01 | 瑞孚信江苏药业股份有限公司 | 一种度鲁特韦中间体的合成方法 |
CN117624404B (zh) * | 2024-01-25 | 2024-03-29 | 默普生物科技(山东)有限公司 | 一种提升葡聚糖硫酸钠化学稳定性与生物活性的合成工艺 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE11037T1 (de) * | 1981-10-01 | 1985-01-15 | Lonza Ag | Verfahren zur herstellung von 4alkoxyacetessigestern. |
DE69933526D1 (de) * | 1998-12-07 | 2006-11-23 | Takasago Perfumery Co Ltd | Verfahren zur Herstellung von optisch aktiven Oxazolidinonderivate |
CA2795350C (en) * | 2010-04-05 | 2016-02-09 | Mannkind Corporation | Ire-1.alpha. inhibitors |
CN104478719B (zh) * | 2015-01-23 | 2016-08-10 | 河南师范大学 | 一种4-甲氧基乙酰乙酸甲酯的制备方法 |
-
2015
- 2015-12-04 CN CN201710490010.1A patent/CN107311861B/zh active Active
- 2015-12-04 CN CN201510877720.0A patent/CN105481694B/zh not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN107311861A (zh) | 2017-11-03 |
CN107311861B (zh) | 2020-04-21 |
CN105481694A (zh) | 2016-04-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105481694B (zh) | 一种4‑甲氧基乙酰乙酸乙酯的合成方法 | |
CN101193880B (zh) | 喜巴辛类似物的外型和非对映立体选择合成 | |
CN102875587B (zh) | 一种利用多硫化钠合成含硫硅烷偶联剂的方法 | |
CN103382160B (zh) | 碘帕醇的合成及其合成中间体的制备 | |
CN108586178B (zh) | 腈及其相应胺的制造方法 | |
CN104478719B (zh) | 一种4-甲氧基乙酰乙酸甲酯的制备方法 | |
CN103130657A (zh) | 一种2-氯-4-氨基苯酚的合成方法 | |
CN102898328B (zh) | 偶氮二甲酸二乙酯及其中间体的合成方法 | |
CN112094296B (zh) | 一种双(2,4,6-三甲基苯甲酰基)苯基氧化膦的制备方法 | |
CN105418420A (zh) | 一种4-甲氧基乙酰乙酸甲酯的合成方法 | |
JP5090923B2 (ja) | アミノ−またはヒドロキシベンゾニトリルの製造方法 | |
CN102250029A (zh) | 一种三嗪羟乙基乙二胺基多元羧酸的制备方法 | |
CN101450895A (zh) | 三氟苯乙酸的制备方法 | |
CN103497117B (zh) | 乙二胺四乙酸的生产工艺 | |
CN103012473B (zh) | 一种双甘膦的合成方法 | |
CN105745191A (zh) | 一种西洛多辛及其中间体的制备方法 | |
WO2010114151A1 (ja) | アルコール化合物の製造方法およびその触媒 | |
CN107513025A (zh) | 一种脂肪酸二乙醇酰胺的合成方法 | |
CN103992241B (zh) | N-取代苯基甘氨酸的制备方法 | |
CN109293478B (zh) | 一种制备四氟苯甲醇的方法 | |
CN100560558C (zh) | 一种2,3,5,6-四氟苯甲酸的制备方法 | |
CN106167469A (zh) | 一种合成2‑氨基‑4,6‑二羟基嘧啶的方法 | |
CN104496842B (zh) | 受阻酚类抗氧剂1019的制备方法 | |
JPWO2015012271A1 (ja) | 複素環化合物の製造方法 | |
CN103880760A (zh) | 一种5-三氟甲基尿嘧啶的合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170519 Address after: 18-812 room 213000, South Tongjiang Road, bell tower area, Changzhou, Jiangsu Applicant after: Changzhou Peng Bo intellectual property services Co., Ltd. Address before: 453007 Xinxiang East Road, Makino District, Henan, No. 46 Applicant before: Henan Normal University |
|
TA01 | Transfer of patent application right | ||
CB03 | Change of inventor or designer information |
Inventor after: Ye Fangguo Inventor after: Zhao Zhongwei Inventor after: Hu Jingbo Inventor before: Li Wei Inventor before: Mu Kairui Inventor before: Suo Huajun Inventor before: Mao Longfei Inventor before: Xu Guiqing Inventor before: Guo Jingjing Inventor before: Chen Changpo |
|
CB03 | Change of inventor or designer information | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170724 Address after: 238251 Ma'anshan town and Wujiang Town, Anhui province Anhui fine chemical industry base Applicant after: Anhui Huachang high tech Pharmaceutical Co., Ltd. Address before: 18-812 room 213000, South Tongjiang Road, bell tower area, Changzhou, Jiangsu Applicant before: Changzhou Peng Bo intellectual property services Co., Ltd. |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170825 Termination date: 20191204 |
|
CF01 | Termination of patent right due to non-payment of annual fee |