CN105732355A - Preparation method of 1-(5-fluoro-2-iodophenyl)ethanone - Google Patents
Preparation method of 1-(5-fluoro-2-iodophenyl)ethanone Download PDFInfo
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- CN105732355A CN105732355A CN201610212802.8A CN201610212802A CN105732355A CN 105732355 A CN105732355 A CN 105732355A CN 201610212802 A CN201610212802 A CN 201610212802A CN 105732355 A CN105732355 A CN 105732355A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
Abstract
The invention relates to a preparation method of 1-(5-fluoro-2-iodophenyl)ethanone.According to the method, 2-amino-5-fluorobenzoic acid and 5-fluoro-2-iodobenzoic acid react to prepare the final product 1-(5-fluoro-2-iodophenyl)ethanone.The method is simple and convenient to implement, mild in reaction condition, high in safety and particularly suitable for industrial production; the product is high in yield and purity.
Description
[technical field]
The present invention relates to the preparation method of a kind of 1-(5-fluoro-2-iodophenyl) ethyl ketone.
[background technology]
Cancer is the key factor causing mankind's death because of disease, and the kind of cancer comprises a lot, according to system
Counting it is one of former world major causes of death.The generation of cancer is by series of complex multiple genetic and molecule thing
Part, comprises the factor such as gene mutation, chromosome translocation and causes.In order to meet the needs for the treatment of disease, therefore
The research and development of cancer therapy drug, especially change molecular target during treatment of cancer or targeting multiplicity are always full generation
Boundary's pharmacy corporation priority fields of study.
It has been investigated that, fluoro-2,10, the 16-trimethyl-15-side epoxides of compound (10R)-7-amido-12-
-10,15,16,17-tetrahydrochysene-2H-8,4-(methylene) pyrazolo [4,3-h] [2,5,11] benzo oxa-diazacyclo 14
Alkynes-3-formonitrile HCN is a kind of gradually changeable lymphom kinase (ALK) and c-ros oncogene I (ROSI) receptor cheese
The strength huge ring inhibitor of histidine kinase wild type and resistant mutants, its compound structure is as follows:
The cancer that in clinic, this medicine is mainly used in include pulmonary carcinoma, osteocarcinoma, skin carcinoma, head and neck cancer, skin or
Ophthalmic melanoma, uterus carcinoma, ovarian cancer, rectal cancer, gastric cancer, the esophageal carcinoma, lymphatic lymphatic cancer,
Nonsmall-cell lung cancer, neuroblastoma etc..
1-(5-fluoro-2-iodophenyl) ethyl ketone is synthesis Compound Compound (10R)-7-amido-12-fluoro-2,10,16-front three
Base-15-side Oxy-1 0,15,16,17-tetrahydrochysene-2H-8,4-(methylene) pyrazolo [4,3-h] [2,5,11] benzo oxa-two
A kind of important intermediate of azacyclo-14 alkynes-3-formonitrile HCN, its molecular weight is 264.035, and structural formula is as follows:
[summary of the invention]
It is an object of the invention to provide the method that one efficiently prepares 1-(5-fluoro-2-iodophenyl) ethyl ketone, improve and produce
Thing yield and purity, the method reaction condition gentleness is simple to operation.
To achieve these goals, it is provided that the preparation method of a kind of 1-(5-fluoro-2-iodophenyl) ethyl ketone, including following
Step:
Step 1) 2-amino-5-fluorobenzoic acid is added in the concentrated sulfuric acid aqueous solution prepared, maintain the temperature at
Stir at 0～10 DEG C, the aqueous solution of dropping sodium nitrite, stir to reactant liquor without solid, TLC (PE/EA:1/1)
After monitoring reaction terminates, adding carbamide, stirring is cooled to 0 DEG C, rapidly joins 0 DEG C containing liquor kalii iodide, liter
To room temperature, agitation and filtration, washing obtains brown solid；By solid with ethyl acetate dissolve, successively with hydrochloric acid,
Sodium bisulfate, saturated aqueous common salt wash, and are dried, and steam solvent, add toluene, then it is molten to steam ethyl acetate
Agent, cooling obtains 5-fluoro-2-iodo-benzoic acid；
Step 2) the 5-fluoro-2-iodo-benzoic acid obtained is added in thionyl chloride solvent, it is heated to 60 DEG C, stirs
Mixing and clarify to reactant liquor, solvent evaporated, addition toluene is evaporated, and acetic acid ethyl dissolution is standby；By malonic acid two
Ethyl ester adds in ethyl acetate, adds magnesium chloride, room temperature reaction 30 minutes while stirring, drips triethylamine,
Drip off stirring 30 minutes, be cooled to 5～10 DEG C, drip above-mentioned acyl chlorides, stir 2 hours under room temperature, reaction knot
Shu Hou, under frozen water cooling, adds 2N hydrochloric acid, separatory, and organic facies saturated aqueous common salt washs, and separates, and steams
Dried organic layer, obtains red oil, add prepared acetic acid, concentrated sulphuric acid mixed aqueous solution in, add
Heat, to 100 DEG C, stirs, and boils off acetic acid, adds EA/ aqueous solution, and extraction, organic facies uses sodium hydroxide successively
Solution, saturated aqueous common salt wash, and dry being evaporated obtains red oil, cross silicagel column (PE/EA:8/1) and obtain
To 1-(5-fluoro-2-iodophenyl) ethyl ketone.
Mixed solution A described in above-mentioned reaction is concentrated sulphuric acid and water volume ratio is the solution of 1:7.8.
Described in above-mentioned reaction containing the solution solvent of potassium iodide be concentrated sulphuric acid be the solution of 1:9.3 with water volume ratio.
Wash as using 6N hydrochloric acid successively with hydrochloric acid, sodium bisulfate, saturated aqueous common salt successively described in above-mentioned reaction
Washing 3 times, 10%NaHSO3 washs 2 times, and saturated aqueous common salt washs 3 times.
During dripping acyl chlorides in above-mentioned reaction, temperature controls at 0～10 DEG C.
The nitration mixture B prepared described in above-mentioned reaction is acetic acid: water: concentrated sulphuric acid volume ratio is 6.6:4.4:
The solution of 1.
EA/ aqueous solution described in above-mentioned reaction is EA and water volume ratio is the solution of 1:1.
It is 0.5N hydrogen that organic facies described in above-mentioned reaction is washed with sodium hydroxide solution, saturated aqueous common salt successively
Sodium hydroxide solution is washed 1 time, and saturated aqueous common salt washs 2 times.
It is highly preferred that described 1-(5-fluoro-2-iodophenyl) ethyl ketone preparation method is as follows:
2-amino-5-fluorobenzoic acid is added by the mixing of the solution preparation that concentrated sulphuric acid and water volume ratio are 1:7.8
In solution, maintain the temperature at and stir at 0～10 DEG C, the aqueous solution of the sodium nitrite of dropping 5.64mol/L, stirs
Mixing to reactant liquor without solid, after TLC (PE/EA:1/1) monitoring reaction terminates, add carbamide, stirring is cooled to
0 DEG C, rapidly join the solvent of 0 DEG C be concentrated sulphuric acid with water volume ratio be 1:9.3 containing liquor kalii iodide, slowly
Being warming up to room temperature, be stirred overnight, filter, washing obtains brown solid.By molten for solid with ethyl acetate solution
Solve, wash 3 times with 6N salt acid elution 3 times, 10% sodium bisulfate washing 2 times, saturated aqueous common salt successively,
Being dried, steam major part solvent, add toluene, then steam residual acetic acid ethyl ester, cooling obtains 5-fluoro-2-iodine
Benzoic acid.
Fluoro-for 5-2-iodo-benzoic acid is added in 13.87mol/L thionyl chloride solvent, is heated to 60 DEG C, stirred
Night clarifies completely to reactant liquor, after TLC (PE/EA:10/1) monitoring reaction terminates, and solvent evaporated, add first
Benzene is evaporated, and acetic acid ethyl dissolution is standby.
Diethyl malonate is added in ethyl acetate, add magnesium chloride while stirring, room temperature reaction 30 minutes,
Dropping triethylamine, drips off stirring 30 minutes, is cooled to 5～10 DEG C, drips above-mentioned acyl chlorides, add and stir under room temperature
Mix 2 hours, after TLC (PE/EA:10/1) monitoring reaction terminates, under frozen water cooling, add 2N hydrochloric acid,
Separatory, organic facies saturated aqueous common salt washs, and separates, is evaporated organic layer, obtains red oil, adds
By acetic acid: water: concentrated sulphuric acid volume ratio is in the mixed acid solution of 6.6:4.4:1 configuration, is heated to 100 DEG C,
Being stirred overnight, boil off acetic acid, add in the EA/ aqueous solution that volume ratio is 1:1 and extract, organic facies depends on
The sodium hydroxide solution washing 1 time of secondary 0.5N, saturated aqueous common salt wash 2 times, and dry being evaporated obtains redness
Grease, crosses quick silicagel column (PE/EA:8/1) and obtains product 1-(5-fluoro-2-iodophenyl) ethyl ketone.
The present invention provide method, final production yield and purity can not only be significantly improved, also have simple to operate,
Reaction time is short, safely and efficiently advantage be particularly suitable for industrialized production.
[accompanying drawing explanation]
Fig. 1 is the reactions steps route map of the present invention.
[detailed description of the invention]
Unless otherwise defined, skill belonging to the present invention uses all technology and implication and the present invention of scientific terminology
The implication that art field those of ordinary skill is generally understood that is identical.Generally, the present invention use name and following reality
Proved recipe method is all well known in the art or conventional, if not specializing, and examination used in the embodiment of the present invention
Test agent and material are all commercially available.In order to make technical problem solved by the invention, technical scheme and have
Benefit effect is clearer, and below in conjunction with specific embodiment, the present invention is further illustrated.
The middle 2-amino-5-fluorobenzoic acid that reaction of the present invention uses is as shown in Equation 1
Compound shown in formula 1 derives from commercially available, cheap and easy to get.
Reactions steps route in the present embodiment is as shown in Figure 1.
Embodiment 1:
In the 20.3L mixed solution A that the 2-amino-5-fluorobenzoic acid addition of 3.0kg has been prepared (concentrated sulphuric acid/
Water is 2.3L/18L), maintain the temperature at and stir at 5 DEG C, the 5.64mol/L sodium nitrite of dropping 3.6L is water-soluble
Liquid, stirs to reactant liquor without solid, after TLC (PE/EA:1/1) monitoring reaction terminates, adds 116g carbamide,
Stirring 15 minutes, be cooled to 0 DEG C, the solvent of rapidly join 10.3L 0 DEG C is that concentrated sulphuric acid is with water volume ratio
1:9.3 containing 4.5Kg liquor kalii iodide, be to slowly warm up to room temperature, be stirred overnight, filter, washing obtains
Brown solid.By solid with 30L ethyl acetate solution dissolve, successively with 6N hydrochloric acid (5L × 3) washing, 10%
Sodium bisulfate (5L × 2) washing, saturated aqueous common salt (5L × 3) washing, be dried, steam about 25L solvent, add
20L toluene, then steam residual acetic acid ethyl ester, cooling obtains 4.5Kg5-fluoro-2-iodo-benzoic acid, its structure such as formula
Shown in 2:
Fluoro-for 4.5Kg5-2-iodo-benzoic acid is added in the 13.87mol/L thionyl chloride solvent of 6L, be heated to
60 DEG C, it is stirred overnight and clarifies completely to reactant liquor, after TLC (PE/EA:10/1) monitoring reaction terminates, be evaporated
Solvent, adds 5L toluene and is evaporated, and 5L acetic acid ethyl dissolution is standby.
3658g diethyl malonate is added in 55L ethyl acetate, adds 4762g magnesium chloride while stirring,
Room temperature reaction 30 minutes, drips 4877g triethylamine, drips off stirring 30 minutes, is cooled to 5 DEG C, in dropping
Stating acyl chlorides, add and stir 2 hours under room temperature, after TLC (PE/EA:10/1) monitoring reaction terminates, frozen water is cold
But under, adding 2N hydrochloric acid (5L × 2), separatory, organic facies saturated aqueous common salt (10L × 2) washs, and separates, and steams
Dried organic layer, obtains red oil, adds 12L by acetic acid: water: concentrated sulphuric acid volume ratio is 6.6:4.4:
In the mixed acid solution of 1 configuration, being heated to 100 DEG C, be stirred overnight, boil off acetic acid, adding 80L volume ratio is
The EA/ aqueous solution of 1:1 extracts, organic facies successively with the sodium hydroxide solution (30L × 1) of 0.5N,
Saturated aqueous common salt (10L × 2) washs, and dry being evaporated obtains red oil, crosses quick silicagel column (PE/EA:8/1)
Obtain product 3.6Kg1-(5-fluoro-2-iodophenyl) ethyl ketone, its structural formula as shown in Equation 3:
Embodiment 2:
In the 30L mixed solution A that the 2-amino-5-fluorobenzoic acid addition of 4.50kg has been prepared (concentrated sulphuric acid/
Water is 3L/27L), maintain the temperature at and stir at 5 DEG C, the 5.64mol/L sodium nitrite in aqueous solution of dropping 5.4L,
Stir to reactant liquor without solid, after TLC (PE/EA:1/1) monitoring reaction terminates, add 174g carbamide, stir
Mixing 15 minutes, be cooled to 0 DEG C, the solvent of rapidly join 15L 0 DEG C is concentrated sulphuric acid and water volume ratio is 1:
9.3 containing 6.7Kg liquor kalii iodide, be to slowly warm up to room temperature, be stirred overnight, filter, washing obtain brown
Solid.Solid 45L ethyl acetate solution is dissolved, successively with 6N hydrochloric acid (8L × 3) washing, 10% sulphuric acid
Hydrogen sodium (8L × 2) washing, saturated aqueous common salt (8L × 3) washing, be dried, steam about 35L solvent, add 30L
Toluene, then steam residual acetic acid ethyl ester, cooling obtains the 5-fluoro-2-iodo-benzoic acid of 6.7Kg.
Fluoro-for the 5-of 6.7Kg 2-iodo-benzoic acid is added in the 13.87mol/L thionyl chloride solvent of 9L, heating
To 60 DEG C, it is stirred overnight to reactant liquor and clarifies completely, after TLC (PE/EA:10/1) monitoring reaction terminates,
Solvent evaporated, adds 8L toluene and is evaporated, and 8L acetic acid ethyl dissolution is standby.
3650g diethyl malonate is added in 55L ethyl acetate, adds 4760g magnesium chloride while stirring,
Room temperature reaction 30 minutes, drips 4880g triethylamine, drips off stirring 30 minutes, is cooled to 0 DEG C, dropping
The above-mentioned acyl chlorides solvent of 2/3 volume, stirs 2 hours under room temperature, and TLC (PE/EA:10/1) monitors reaction
After end, under frozen water cooling, adding 2N hydrochloric acid (5L × 2), separatory, organic facies is with saturated aqueous common salt (10L × 2)
Washing, separates, is evaporated organic layer, obtains red oil, adds 12L by acetic acid: water: concentrated sulphuric acid body
Long-pending ratio, in the mixed acid solution for 6.6:4.4:1 configuration, is heated to 100 DEG C, is stirred overnight, boil off acetic acid,
Adding in the EA/ aqueous solution that 80L volume ratio is 1:1 and extract, organic facies is successively with the hydrogen-oxygen of 0.5N
Changing sodium solution (30L × 1), saturated aqueous common salt (10L × 2) washing, dry being evaporated obtains red oil, the most quickly
Silicagel column (PE/EA:8/1) obtains 1-(the 5-fluoro-2-iodophenyl) ethyl ketone of product 3.56Kg.
Embodiment 3:
In the 40L mixed solution A that the 2-amino-5-fluorobenzoic acid addition of 6.0kg has been prepared (concentrated sulphuric acid/
Water is 4L/36L), maintain the temperature at and stir at 5 DEG C, the 5.64mol/L sodium nitrite in aqueous solution of dropping 7L,
Stir to reactant liquor without solid, after TLC (PE/EA:1/1) monitoring reaction terminates, add 232g carbamide, stir
Mixing 15 minutes, be cooled to 0 DEG C, the solvent of rapidly join 20L 0 DEG C is concentrated sulphuric acid and water volume ratio is 1:
9.3 containing 9Kg liquor kalii iodide, be to slowly warm up to room temperature, be stirred overnight, filter, it is solid that washing obtains brown
Body.Solid 60L ethyl acetate solution is dissolved, successively with 6N hydrochloric acid (10L × 3) washing, 10% sulphuric acid
Hydrogen sodium (10L × 2) washing, saturated aqueous common salt (10L × 3) washing, be dried, steam about 50L solvent, add 40L
Toluene, then steam residual acetic acid ethyl ester, cooling obtains the 5-fluoro-2-iodo-benzoic acid of 8.9Kg.
Fluoro-for the 5-of 8.9Kg 2-iodo-benzoic acid is added in the 13.87mol/L thionyl chloride solvent of 12L, heating
To 60 DEG C, it is stirred overnight to reactant liquor and clarifies completely, after TLC (PE/EA:10/1) monitoring reaction terminates,
Solvent evaporated, adds 10L toluene and is evaporated, and 10L acetic acid ethyl dissolution is standby.
3650g diethyl malonate is added in 55L ethyl acetate, adds 4760g0 magnesium chloride while stirring,
Room temperature reaction 30 minutes, drips 4880g triethylamine, drips off stirring 30 minutes, is cooled to 10 DEG C, dropping
The above-mentioned acyl chlorides solvent of half volume, stirs 2 hours under room temperature, and TLC (PE/EA:10/1) monitors reaction
After end, under frozen water cooling, adding 2N hydrochloric acid (5L × 2), separatory, organic facies is with saturated aqueous common salt (10L × 2)
Washing, separates, is evaporated organic layer, obtains red oil, adds 12L by acetic acid: water: concentrated sulphuric acid body
Long-pending ratio, in the mixed acid solution for 6.6:4.4:1 configuration, is heated to 100 DEG C, is stirred overnight, boil off acetic acid, adds
80L volume ratio be 1:1 EA/ aqueous solution in extract, organic facies is molten with the sodium hydroxide of 0.5N successively
Liquid (30L × 1), saturated aqueous common salt (10L × 2) wash, and dry being evaporated obtains red oil, crosses quick silicagel column
(PE/EA:8/1) 1-(the 5-fluoro-2-iodophenyl) ethyl ketone of product 3.58Kg is obtained.
It should be noted that, although the present invention is disclosed above with preferred embodiment, so it is not limited to this
Invention, any is familiar with this those skilled in the art, and without departing from the spirit and scope of the present invention, that is made any repaiies
Change, equivalent and improvement etc., should be included within the scope of the present invention.
Claims (7)
1. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone, it is characterised in that comprise the following steps:
Step 1) 2-amino-5-fluorobenzoic acid is added in the concentrated sulfuric acid aqueous solution prepared, maintain the temperature at
Stir at 0～10 DEG C, the aqueous solution of dropping sodium nitrite, stir to reactant liquor without solid,
After TLC (PE/EA:1/1) monitoring reaction terminates, adding carbamide, stirring is cooled to 0 DEG C, rapidly joins 0 DEG C
Containing liquor kalii iodide, being warmed to room temperature, agitation and filtration, washing obtains brown solid；Solid is used acetic acid second
Ester dissolves, and successively with hydrochloric acid, sodium bisulfate, saturated aqueous common salt washing, is dried, steams solvent, add
Toluene, then steam ethyl acetate solvent, cooling obtains 5-fluoro-2-iodo-benzoic acid；
Step 2) the 5-fluoro-2-iodo-benzoic acid obtained is added in thionyl chloride solvent, it is heated to 60 DEG C, stirring
Clarifying to reactant liquor, solvent evaporated, add toluene and be evaporated, acetic acid ethyl dissolution is standby；By malonic acid two
Ethyl ester adds in ethyl acetate, adds magnesium chloride, room temperature reaction 30 minutes while stirring, drips triethylamine,
Drip off stirring 30 minutes, be cooled to 5～10 DEG C, drip above-mentioned acyl chlorides, stir 2 hours under room temperature, reaction
After end, under frozen water cooling, adding 2N hydrochloric acid, separatory, organic facies saturated aqueous common salt washs, and separates,
Be evaporated organic layer, obtain red oil, add prepared acetic acid, concentrated sulphuric acid mixed aqueous solution in,
It is heated to 100 DEG C, stirring, boil off acetic acid, add EA/ aqueous solution, extraction, organic facies uses hydrogen-oxygen successively
Changing sodium solution, saturated aqueous common salt washing, dry being evaporated obtains red oil, crosses silicagel column (PE/EA:8/1)
Obtain 1-(5-fluoro-2-iodophenyl) ethyl ketone.
2. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone as claimed in claim 1, it is characterised in that step 1)
Middle concentrated sulphuric acid: water volume ratio is 1:7.8.
3. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone as claimed in claim 1, it is characterised in that step 1)
In the solvent of solution containing potassium iodide be concentrated sulphuric acid: water volume ratio is the solution of 1:9.3.
4. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone as claimed in claim 1, it is characterised in that step 1)
Described in successively with hydrochloric acid, sodium bisulfate, saturated aqueous common salt washing for successively with 6N salt acid elution,
10%NaHSO3Washing, saturated aqueous common salt washs.
5. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone as claimed in claim 1, it is characterised in that step 2)
Described in EA/ aqueous solution be EA and water volume ratio is the solution of 1:1.
6. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone as claimed in claim 1, it is characterised in that step 2)
Described in organic facies successively with sodium hydroxide solution, saturated aqueous common salt washing be 0.5N sodium hydroxide solution
Washing and saturated aqueous common salt wash.
7. the preparation method of 1-(5-fluoro-2-iodophenyl) ethyl ketone as claimed in claim 1, it is characterised in that:
Step 1) 2-amino-5-fluorobenzoic acid is added by the solution preparation that concentrated sulphuric acid and water volume ratio are 1:7.8
In mixed solution, maintain the temperature at and stir at 0～10 DEG C, the aqueous solution of the sodium nitrite of dropping 5.64mol/L,
Stirring to reactant liquor without solid, after reaction terminates, add carbamide, stirring is cooled to 0 DEG C, quickly adds
Enter the solvent of 0 DEG C be concentrated sulphuric acid with water volume ratio be 1:9.3 containing liquor kalii iodide, be warmed to room temperature, stirring
Filtering, washing obtains brown solid；Solid with ethyl acetate solution is dissolved, successively with 6N salt acid elution
3 times, 10% sodium bisulfate wash 2 times, saturated aqueous common salt wash 3 times, be dried, steam major part solvent,
Adding toluene, then steam residual acetic acid ethyl ester, cooling obtains 5-fluoro-2-iodo-benzoic acid；
Step 2) fluoro-for 5-2-iodo-benzoic acid is added in 13.87mol/L thionyl chloride solvent, it is heated to 60 DEG C, stirs
Mixing and clarify to reactant liquor, after reaction terminates, solvent evaporated, addition toluene is evaporated, and acetic acid ethyl dissolution is standby
With；Diethyl malonate is added in ethyl acetate, add magnesium chloride, room temperature reaction 30 points while stirring
Clock, drips triethylamine, drips off stirring 30 minutes, is cooled to 5～10 DEG C, drips above-mentioned acyl chlorides, add room
The lower stirring of temperature 2 hours, after reaction terminates, under frozen water cooling, adds 2N hydrochloric acid, separatory, and organic facies is used
Saturated aqueous common salt washs, and separates, is evaporated organic layer, obtains red oil, adds by acetic acid: water:
Concentrated sulphuric acid volume ratio is in the mixed acid solution of 6.6:4.4:1 configuration, is heated to 100 DEG C, and stirring boils off vinegar
Acid, adds in the EA/ aqueous solution that volume ratio is 1:1 and extracts, and organic facies is successively with the hydrogen-oxygen of 0.5N
Changing sodium solution, saturated aqueous common salt washing, dry being evaporated obtains red oil, crosses silicagel column (PE/EA:8/1)
Obtain product 1-(5-fluoro-2-iodophenyl) ethyl ketone.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20130196952A1 (en) * | 2010-05-04 | 2013-08-01 | Pfizer Inc. | Heterocyclic derivatives for the treatment of diseases |
| CN104169286A (en) * | 2012-03-06 | 2014-11-26 | 辉瑞大药厂 | Macrocyclic derivatives for the treatment of proliferative diseases |
| WO2015031650A1 (en) * | 2013-08-28 | 2015-03-05 | Sarvajit Chakravarty | Heterocyclic compounds and methods of use |
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2016
- 2016-04-07 CN CN201610212802.8A patent/CN105732355A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130196952A1 (en) * | 2010-05-04 | 2013-08-01 | Pfizer Inc. | Heterocyclic derivatives for the treatment of diseases |
| CN104169286A (en) * | 2012-03-06 | 2014-11-26 | 辉瑞大药厂 | Macrocyclic derivatives for the treatment of proliferative diseases |
| WO2015031650A1 (en) * | 2013-08-28 | 2015-03-05 | Sarvajit Chakravarty | Heterocyclic compounds and methods of use |
Non-Patent Citations (1)
| Title |
|---|
| XIAO HU等: "Copper-catalyzed ligand-free amidation of aryl iodides and amino acid amides to synthesize C3-(Z)-1H-benzo[e][1,4]diazepin-2(3H)-ones", 《MOLECULAR DIVERSITY》 * |
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Application publication date: 20160706 |