CN1849298A - Production of N-acyl compounds - Google Patents
Production of N-acyl compounds Download PDFInfo
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- CN1849298A CN1849298A CNA2004800261472A CN200480026147A CN1849298A CN 1849298 A CN1849298 A CN 1849298A CN A2004800261472 A CNA2004800261472 A CN A2004800261472A CN 200480026147 A CN200480026147 A CN 200480026147A CN 1849298 A CN1849298 A CN 1849298A
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- compound
- nitrogen
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- acid
- acyl group
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- 238000000034 method Methods 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 17
- 230000010933 acylation Effects 0.000 claims description 13
- 238000005917 acylation reaction Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 9
- -1 chloro- Chemical class 0.000 claims description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-Phenylalanine Natural products OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 7
- 229960005190 phenylalanine Drugs 0.000 claims description 7
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 6
- 125000005252 haloacyl group Chemical group 0.000 claims description 5
- 229910017464 nitrogen compound Inorganic materials 0.000 claims description 5
- 150000002830 nitrogen compounds Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229940024606 amino acid Drugs 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 150000001266 acyl halides Chemical class 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 3
- 239000012433 hydrogen halide Substances 0.000 claims description 3
- 150000004702 methyl esters Chemical class 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229930182817 methionine Natural products 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 229930182832 D-phenylalanine Natural products 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001263 acyl chlorides Chemical class 0.000 abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 abstract 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- 150000001412 amines Chemical class 0.000 description 8
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 7
- 239000002994 raw material Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 5
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 5
- SWVMLNPDTIFDDY-FVGYRXGTSA-N methyl (2s)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=CC=C1 SWVMLNPDTIFDDY-FVGYRXGTSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- VSDUZFOSJDMAFZ-SECBINFHSA-N methyl (2r)-2-amino-3-phenylpropanoate Chemical compound COC(=O)[C@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-SECBINFHSA-N 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- GBVJKFSXRGIZBB-PVSSEACSSA-N (2s)-2-amino-3-phenylpropanoic acid;methyl (2s)-2-amino-3-phenylpropanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.COC(=O)[C@@H](N)CC1=CC=CC=C1 GBVJKFSXRGIZBB-PVSSEACSSA-N 0.000 description 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 230000006181 N-acylation Effects 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000006035 Tryptophane Substances 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- VVSHAVUWLGOYPG-UHFFFAOYSA-N acetyl chloride;2,2,2-trifluoroacetic acid Chemical compound CC(Cl)=O.OC(=O)C(F)(F)F VVSHAVUWLGOYPG-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229940093740 amino acid and derivative Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 238000005583 trifluoroacetylation reaction Methods 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention relates to the production of compounds containing an acylated nitrogen atom. According to said method, the N-protonated adduct of the compounds is reacted with a chloride, bromide or iodide anion, or the free nitrogen base is reacted with acyl halogenide, preferably acyl chloride, in the presence of an acid that expulses the released HCl or Hl.
Description
The present invention relates to a kind of method of compound of the N-of preparation acylations.
The acylations of amine and acyl chlorides is a kind of known response, referring to organic chemistry method (Houben-Weyl), and 4 editions (1958), chapters and sections XI/2,10 and 11 and 30 to 34 pages.Hydrogenchloride dissociates in the reaction, and it combines with second amine molecule, forms amine hydrochlorate.Therefore, the amine that consumes half is used in conjunction with the hydrochloric acid that discharges.If want amine is converted into acid amides fully, must be otherwise in conjunction with free hydrogenchloride, for example by adding the alkaline carbonate of fine-powdered.Perhaps can sneak into pyridine as acid binding agent.Point out 34 pages of the textbook of quoting, though Acetyl Chloride 98Min. is effective acetylation reagent for amine, but commonly used a little be to use as diacetyl oxide because it is easy to use, and always very near one's destination.The objective of the invention is to, a kind of short-cut method for preparing the compound of nitrogen-atoms acylations is provided.This purpose is achieved by the inventive method.
The inventive method comprises that preparation has the compound of nitrogen-atoms of acyl substituted, and initial compounds is corresponding nitrogen compound and the acyl halide with the protonated adducts form of chloro-, bromo-or iodo-negatively charged ion, N-, the preferred acyl chlorides of described acyl halide; Acylations is carried out in the presence of the carboxylic acid corresponding with used acyl group.Nitrogen-atoms must have at least one other hydrogen atom except proton; Perhaps from the free nitrogen base, but must be on the nitrogen-atoms in conjunction with at least 1 hydrogen atom.Term " acyl group " is expressed as radicals R C (O), and wherein R represents: the straight or branched alkyl that has 1 to 6 carbon atom; Phenyl; The straight or branched alkyl that has 1 to 6 carbon atom that is replaced by one or more halogen atoms; The perhaps phenyl that is replaced by one or more halogen atoms.Acyl group is preferably halo acyl group, particularly trifluoroacetyl group, difluoro ethanoyl, chlorine difluoro ethanoyl, C
2F
5C (O), C
2HF
4C (O) or C
2ClF
4C (O).More especially preferably carry out the trifluoro acylations, and corresponding acid is trifluoroacetic acid.
In principle, can any nitrogen compound of acylations, for example amine or its hydrogen halide adducts or carboxylic acid amide.Adopting the preferred nitrogen compound of the inventive method acylations is the amino acid or derivatives thereof, for example ester or peptide.More especially preferably use the inventive method to prepare the amino acid ester or the peptide of N-acylations, especially have trifluoroacetyl group.Can also use the hydrogen halide adducts, preferred hydrogenchloride perhaps has the compound of free N-atom.
Adopt the inventive method can make acid amides, for example use or be used for chemosynthesis with itself.A kind of commodity trifluoroacetamide for example can be used for chemosynthesis.
Even from the characteristic angle, introducing acyl group or halo acyl group also are significant as the blocking group of nitrogen-atoms, especially in chemosynthesis.Particularly, trifluoroacetyl group is known blocking group, for example referring to U.S. Pat 5,541, and 206,6 hurdles.
More especially preferably use the inventive method to amino acid and derivative thereof, especially ester and peptide carry out acylations, particularly the trifluoro acylations.
This application purpose is fit to preparation N-TFA base L-phenylalanine alkyl ester, N-TFA base-D-phenylalanine alkyl ester and N-acyl group-Methionin alkyl ester (omega-amino-), particularly methyl esters and ethyl ester very much.Can also acylations ester (particularly carrying out) with the trifluoro acyl group; alkyl ester particularly; particularly glycine, L-Ala, Xie Ansuan, leucine, Isoleucine, phenylalanine, tyrosine, proline(Pro), hydrogen proline(Pro), Serine, Threonine, halfcystine, Gelucystine, methionine(Met), tryptophane, aspartic acid, L-glutamic acid, the methyl esters of arginine and Histidine and ethyl ester.
Phenylalanine compound is the intermediate product that is fit to, and for example prepares U.S. Pat 5,541,206 or 4,816, and the compound described in 484.
Can separate the compound of the acylations that obtains according to the present invention according to ordinary method.A kind of most suitable method particularly makes compound solidify, and is described in the international patent application of undocumented application number PCT/EP 03/02453.The organic compound that contains the reaction mixture of impurity and fusing point＞30 ℃ is heated, so that evaporate impurity.Then the organic compound that keeps is placed on the refrigerative travelling belt.This method also can be used for the compound that the inventive method obtains.
The invention has the advantages that does not have hydrogenchloride to produce and must remove out.
Further explain the present invention by following examples.
Embodiment
Abbreviation:
MeOH=methyl alcohol
The solution of MeOH*HCl=methyl alcohol and HCl
TFA=trifluoroacetic acid
TFAC=trifluoroacetyl chloride
Embodiment 1:
Prepare L-phenylalanine methyl ester-hydrogenchloride by phenylalanine
L-phenylalanine L-phenylalanine methyl ester * HCl
Raw material:
61.6mol(1973.66g) MeOH(32.04g/mol)
9.8mol(352.8g) HCl(36.0g/mol)
3.05mol (503.83g) L-phenylalanine (165.19g/mol)
1.0mol (103.0g) Di Iso Propyl Ether (102.18g/mol)
Scheme:
In 4 liters of multinecked flasks, be enclosed in the phenylalanine in the solvent, and mix, make it dissolving with the MeOH*HCl solution that makes in advance.For good dissolving more, raw material is heated to 50 ℃, and under reflux (about 55 ℃), boiled about 5 minutes.Drop in the vacuum subsequently, so that distill out remaining MeOH and HCl.Distill the raw material deepening, thickness also forms white floss.After leaving standstill, the sedimentary phenylalanine methyl ester * HCl of suction strainer.Purity is 99.4% (GC), 160 ℃ of boiling points.
As raw material, repeated experiments obtains comparable experimental result with D-or D/L-phenylalanine.
Embodiment 2:
Trifluoroacetylation L-phenylalanine methyl ester-hydrogenchloride
L-phenylalanine methyl ester * HCl N-TFA base-L-phenylalanine methyl ester
Raw material:
2.0mol (435.2g) from L-phenylalanine methyl ester-hydrogenchloride (215.68g/mol) of embodiment 1
7.8mol (889.36g) trifluoroacetic acid (114.02g/mol)
2.6mol (350.5g) trifluoroacetic acid Acetyl Chloride 98Min. (132.47g/mol)
Scheme:
The L-phenylalanine methyl ester (existing) of in 4 liters of multinecked flasks, packing into the HCl-adducts, and be dissolved among the TFA.In dissolution process, raw material slowly is warmed up to 90 ℃.This moment, HCl was free; On bubble counter, can see and produce gas consumingly.Ester dissolve fully and reach temperature after feed TFAC, still emit certain amount of H Cl this moment.
Continue to feed TFAC, all react up to used ester and be N-TFA base-L-phenylalanine methyl ester.Solvent removed in vacuo TFA, the remaining N-TFA base in cooling back-L-phenylalanine methyl ester, 52 ℃ of fusing points, productive rate are 95% of theoretical amount.In an experiment variant scheme, the material that melts is placed on the refrigerative band.This makes that easily loose pellet becomes the product that can well use.
Embodiment 3:
Trifluoroacetyl groupization is from D-phenylalanine methyl ester * HCl and the D/L-phenylalanine methyl ester * HCl of embodiment 1
Use repeats embodiment 2 from D-phenylalanine methyl ester * HCl and the D/L phenylalanine methyl ester * HCl of embodiment 1.Experimental result is corresponding to the result of embodiment 2.
Claims (7)
1, a kind of preparation has the method for compound of the nitrogen-atoms of acylations, and wherein, acyl group is expressed as RC (O), and R represents: the straight or branched alkyl that has 1 to 6 carbon atom; Phenyl; The straight or branched alkyl that is replaced by one or more halogen atoms, have 1 to 6 carbon atom; The perhaps phenyl that is replaced by one or more halogen atoms; this method is to be prepared in the presence of acid from acyl halide and corresponding nitrogen compound; this nitrogen compound is that N-is protonated and treating that at least one other hydrogen atom is arranged on the nitrogen-atoms of acylations; and exist as chloro-, bromo-or iodo-negatively charged ion; perhaps be free alkali form, wherein strength of acid is enough to make formed hydrogen halide to be discharged from reaction mixture.
According to the method for claim 1, it is characterized in that 2, preparation has the compound of halo acyl group-nitrogen groups, the halo acyl group is meant trifluoroacetyl group, difluoro ethanoyl, chlorine difluoro ethanoyl, C
2F
5C (O), C
2HF
4C (O) or C
2ClF
4C (O).
3, according to the method for claim 2, it is characterized in that, in the presence of the halogenated carboxylic acid corresponding, react with this halo acyl group.
4, according to the method for claim 1, it is characterized in that acylated amino acid, its derivative, preferred amino acid ester or peptide.
5, according to the method for claim 1, it is characterized in that preparation trifluoroacetyl based compound in the presence of trifluoroacetic acid.
6, according to the method for claim 1, it is characterized in that the N-TFA based compound of preparation L-phenylalanine alkyl ester, D-phenylalanine alkyl ester or Methionin alkyl ester.
7, according to the method for claim 6, it is characterized in that preparation methyl esters or ethyl ester.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10342261 | 2003-09-11 | ||
| DE10342261.7 | 2003-09-11 | ||
| DE10353116.5 | 2003-11-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1849298A true CN1849298A (en) | 2006-10-18 |
Family
ID=34258634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004800261472A Pending CN1849298A (en) | 2003-09-11 | 2004-08-18 | Production of N-acyl compounds |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1849298A (en) |
| DE (1) | DE10353116A1 (en) |
-
2003
- 2003-11-12 DE DE10353116A patent/DE10353116A1/en not_active Withdrawn
-
2004
- 2004-08-18 CN CNA2004800261472A patent/CN1849298A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE10353116A1 (en) | 2005-04-07 |
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