JPS6354351A - Optically active 1-methyl-3-phenylpropylazide and production of optically active amine using said compound - Google Patents
Optically active 1-methyl-3-phenylpropylazide and production of optically active amine using said compoundInfo
- Publication number
- JPS6354351A JPS6354351A JP19876786A JP19876786A JPS6354351A JP S6354351 A JPS6354351 A JP S6354351A JP 19876786 A JP19876786 A JP 19876786A JP 19876786 A JP19876786 A JP 19876786A JP S6354351 A JPS6354351 A JP S6354351A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- optically active
- formula
- azide
- compound
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 15
- ATSYLQAKLUUERQ-UHFFFAOYSA-N 3-azidobutylbenzene Chemical compound [N-]=[N+]=NC(C)CCC1=CC=CC=C1 ATSYLQAKLUUERQ-UHFFFAOYSA-N 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 title abstract description 5
- 150000001412 amines Chemical class 0.000 title description 2
- -1 sulfonyloxy compound of formula II Chemical compound 0.000 claims abstract description 28
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 9
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 7
- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 8
- 238000006722 reduction reaction Methods 0.000 claims description 6
- WECUIGDEWBNQJJ-UHFFFAOYSA-N 4-phenylbutan-2-amine Chemical compound CC(N)CCC1=CC=CC=C1 WECUIGDEWBNQJJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 230000002255 enzymatic effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 150000001340 alkali metals Chemical class 0.000 abstract description 2
- 239000003880 polar aprotic solvent Substances 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 230000006340 racemization Effects 0.000 abstract description 2
- 239000003905 agrochemical Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- AKGGYBADQZYZPD-UHFFFAOYSA-N benzylacetone Chemical compound CC(=O)CCC1=CC=CC=C1 AKGGYBADQZYZPD-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- WECUIGDEWBNQJJ-VIFPVBQESA-N (2s)-4-phenylbutan-2-amine Chemical compound C[C@H](N)CCC1=CC=CC=C1 WECUIGDEWBNQJJ-VIFPVBQESA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- GDWRKZLROIFUML-UHFFFAOYSA-N 4-phenylbutan-2-ol Chemical compound CC(O)CCC1=CC=CC=C1 GDWRKZLROIFUML-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JJYKJUXBWFATTE-SECBINFHSA-N (2r)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid Chemical compound CO[C@](C(O)=O)(C(F)(F)F)C1=CC=CC=C1 JJYKJUXBWFATTE-SECBINFHSA-N 0.000 description 1
- WECUIGDEWBNQJJ-SECBINFHSA-N (2r)-4-phenylbutan-2-amine Chemical compound C[C@@H](N)CCC1=CC=CC=C1 WECUIGDEWBNQJJ-SECBINFHSA-N 0.000 description 1
- GDWRKZLROIFUML-VIFPVBQESA-N (2s)-4-phenylbutan-2-ol Chemical compound C[C@H](O)CCC1=CC=CC=C1 GDWRKZLROIFUML-VIFPVBQESA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- FWMBBQJILJGRRI-UHFFFAOYSA-N 3-azidopropylbenzene Chemical compound [N-]=[N+]=NCCCC1=CC=CC=C1 FWMBBQJILJGRRI-UHFFFAOYSA-N 0.000 description 1
- MVCLJJYHOMPKMW-UHFFFAOYSA-N 4-azidobutan-2-ylbenzene Chemical compound [N-]=[N+]=NCCC(C)C1=CC=CC=C1 MVCLJJYHOMPKMW-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 101100428830 Caenorhabditis elegans mml-1 gene Proteins 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 108091027881 NEAT1 Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- MLHBZVFOTDJTPK-UHFFFAOYSA-N n-methyl-3-phenylpropan-1-amine Chemical compound CNCCCC1=CC=CC=C1 MLHBZVFOTDJTPK-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、新規光学活性】−メチル−３−フェニルプロ
ピルアジド及びその化合物を用いる光学活性アミンの製
造法に関する。更に詳しくは、−般式
（式中、Ｒ，はメチル、エチル、フェニル、ｐ−メチル
フェニルあるいはベンジル基、米は不ｋＲ素を表わす）
で表わされる光学活性スルホニルオキシ化合物を、アジ
化水素のアルカリ金属塩と反応させ、新規光学活性１−
メチル−３−フェニルプロピルアジドを得、さらにこの
生成物を還元反応に付することを特徴とする光学活性１
−メチル−３−フェニルプロピルアミンの製造法に関す
る。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing optically active amines using novel optically active -methyl-3-phenylpropyl azide and its compounds. More specifically, - general formula (wherein R represents methyl, ethyl, phenyl, p-methylphenyl or benzyl group, and rice represents a non-kR element)
The optically active sulfonyloxy compound represented by is reacted with an alkali metal salt of hydrogen azide to form a novel optically active 1-
Optical activity 1 characterized by obtaining methyl-3-phenylpropyl azide and further subjecting this product to a reduction reaction
-Relating to a method for producing methyl-3-phenylpropylamine.
本発明の方法で得られる光学活性１−メチル−３−フェ
ニルプロピルアミンは、医薬、 ｐ 薬等（７）合成原
料として有用な物質である。The optically active 1-methyl-3-phenylpropylamine obtained by the method of the present invention is a substance useful as a raw material for the synthesis of pharmaceuticals, p-drugs, etc. (7).
従来、光学活性１−メチル−３−フェニルプロピルアミ
ンは、そのラセミ体を光学分割する方法（ジャーナル・
オブ・メディシナル・ケミストリー、２５巻、１３６３
頁（１９８２年）、特開昭５９−１０８７４９など）、
あるいはベンジルアセトンを光学活性α−メチルベンジ
ルアミント反応させ、生ずるイミン化合物を還元するこ
とにより合成する方法（ジャーナル・オブ・メデイシナ
ル・ケミストリー、２５巻、６７０頁（１９８２年）、
特開昭５８−１９４８４７）が知られている。前者のラ
セミ体の光学分割法は操作が煩雑で不用な対掌体を副生
じ、低収率である。後者の合成法は中間体として不用な
ジアステレオマーの除去が困難で収率も低い。Conventionally, optically active 1-methyl-3-phenylpropylamine was obtained by optically resolving its racemic form (Journal.
Of Medicinal Chemistry, Volume 25, 1363
Page (1982), Japanese Patent Application Publication No. 108749/1984, etc.),
Alternatively, a method of synthesizing benzylacetone by subjecting it to an optically active α-methylbenzylamine reaction and reducing the resulting imine compound (Journal of Medicinal Chemistry, Vol. 25, p. 670 (1982),
JP-A-58-194847) is known. The former method of optical resolution of the racemate is complicated, produces unnecessary enantiomers, and has a low yield. In the latter synthetic method, it is difficult to remove unnecessary diastereomers as intermediates, and the yield is low.
光学活性スルホニルオキシ化合物を原料とし、光学活性
■−メチルー３−フェニルプロピルアジドを経由する光
学活性１−メチル−３−フェニルプロピルアミンの製造
法は全く知られていない。There is no known method for producing optically active 1-methyl-3-phenylpropylamine using an optically active sulfonyloxy compound as a raw material and via optically active (1)-methyl-3-phenylpropyl azide.
この合成法が開発でき、更に出発光学活性体の不斉を保
持あるいは反転させ、ラセミ化を起すことなく光学活性
１−メチル−３−フェニルプロピルアミンに変換するこ
とができれば、従来問題でちつた不用な光学活性副生物
を生ずることなく、目的の光学活性体のみを簡便かつ収
率良く得ることが可能となる。If this synthetic method could be developed, and if the chirality of the starting optically active compound could be maintained or reversed and converted to optically active 1-methyl-3-phenylpropylamine without causing racemization, it would be possible to eliminate unnecessary problems caused by conventional problems. It becomes possible to obtain only the desired optically active substance simply and with high yield without producing optically active by-products.
本発明の出発物質である光学活性スルホニルオキシ化合
物の原料となる光学活性１−メチル−３−フェニルプロ
パツールはベンジルアセトンの微生物的不斉還元により
容易にうろことができる。Optically active 1-methyl-3-phenylpropanol, which is a raw material for the optically active sulfonyloxy compound that is the starting material of the present invention, can be easily isolated by microbial asymmetric reduction of benzylacetone.
通常の微生物の培養培地に、例えばキャンディダ・ギエ
ルモンデイＩＦＯ０６７９、あるいはビキャ・ファリノ
ーサＩＪ”００９９１を植菌し、好気的に培養する。培
養終了後、菌体を遠心分離により集め、１．５１！の水
に懸濁し、ベンジルアセトンを添加し、ｐＨをＮａＯＨ
で６．０に保ちながら３０℃で反応させ、反応終了後、
等量のへ１：酸エチルで２回抽出する。酢酸エチル層を
無水芒硝で脱水したのち減圧上脱溶剤し、これを蒸留す
れば無色オイル状の（ｓ）−ｉ−メチル−３−フェニル
プロパノールアルいハ（Ｉυ−１−メチル−３−フェニ
ルプロパツールを得ることができる。For example, Candida guillermondei IFO0679 or Vicha farinosa IJ"00991 is inoculated into a normal microorganism culture medium and cultured aerobically. After the culture is completed, the bacterial cells are collected by centrifugation and 1.51! of water, add benzyl acetone and adjust the pH to NaOH.
The reaction was carried out at 30°C while maintaining the temperature at 6.0, and after the reaction was completed,
Extract twice with equal volumes of 1:ethyl acetate. After dehydrating the ethyl acetate layer with anhydrous sodium sulfate and removing the solvent under reduced pressure, distilling this gives (s)-i-methyl-3-phenylpropanol alcohol (Iυ-1-methyl-3-phenyl) as a colorless oil. You can get property tools.
次に、この光学活性１−メチル−３−フェニルプロパツ
ールと、塩化スルホニル誘導体、たとえばメシルクロラ
イド、エタンスルホニルクロライド、フェニルスルホニ
ルクロライドあるいはトシルクロライド等の塩化スルホ
ニル誘導体とを、塩基（たとえばトリエチルアミン）の
存在下、反応させることにより光学活性有機スルホニル
オキシ化合物を得ることができる。Next, this optically active 1-methyl-3-phenylpropanol and a sulfonyl chloride derivative such as mesyl chloride, ethanesulfonyl chloride, phenylsulfonyl chloride or tosyl chloride are mixed in the presence of a base (for example triethylamine). An optically active organic sulfonyloxy compound can be obtained by the following reaction.
本発明者らは、光学活性スルホニルオキシ化合物のアジ
ド化法及び光学活性１−メ°チルー３−フェニルプロピ
ルアジドの還元法を鋭意検討しｆ、＝結果、ラセミ化す
ることなく、収率良く光学活性ＩＪチルー３−フェニル
プロピルアミンを合成スる方法を見い出し本発明を完成
した。The present inventors have intensively studied the azidation method of optically active sulfonyloxy compounds and the reduction method of optically active 1-methyl-3-phenylpropyl azide, and found that the optical The present invention was completed by discovering a method for synthesizing active IJ-3-phenylpropylamine.
新規光学活性体である１−メチル−３−フェニルプロピ
ルアジドは、一般式
（式中、Ｒはメチル、エチル、フェニル、ｐ−メチルフ
ェニルあるいはベンジル基、米は不斉炭素を表わす）で
表わされる光学活性スルホニルオキシ化合物を、アジ化
水素のアルカリ金属塩と反応させることにより取得でき
る。1-Methyl-3-phenylpropyl azide, a new optically active substance, is represented by the general formula (wherein R represents methyl, ethyl, phenyl, p-methylphenyl or benzyl group, and R represents an asymmetric carbon). An optically active sulfonyloxy compound can be obtained by reacting with an alkali metal salt of hydrogen azide.
アルカリ金属としてはリチウム、ナトリウム。Alkali metals include lithium and sodium.
カリウムを用いることができるが、ナトリウムが望まし
い。反応は、極性非プロトン性溶剤中で容易に進行し、
ジメチルスルホキシド、Ｎ、Ｎ−ジメチルホルムアミド
、Ｎ、Ｎ−ジメチルアセトアミドあるいはアセトニトリ
ル等が使用できる。アジ化水素のアルカリ金属塩は、光
学活性スルホニルオキシ化合物に対して１．０倍モル以
上使用すれば良いが、通常１．１〜２，０倍モルが用い
られる。反応は室温下でも進行するが、３０〜７０℃に
加熱することにより速かに進行させることができる。Potassium can be used, but sodium is preferred. The reaction proceeds easily in polar aprotic solvents,
Dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide or acetonitrile can be used. The alkali metal salt of hydrogen azide may be used in an amount of at least 1.0 times the mole of the optically active sulfonyloxy compound, but it is usually used in an amount of 1.1 to 2.0 times the mole. Although the reaction proceeds at room temperature, it can be accelerated by heating to 30 to 70°C.
■−メチルー３−フェニルプロピルアジドのρ元反応は
、メタノール、エタノール、ジオキサン。■-Methyl-3-phenylpropyl azide's primary reaction is methanol, ethanol, and dioxane.
テトラヒドロフラン、酢酸エチル、水、あるいはこれら
の混合物を溶剤として、常圧〜散気圧の水素雰囲気下で
白金、パラジウム、ニッケル等の金属触媒を用いる方法
が利用される。反応温度は０〜６０℃の範囲が望ましい
。またエーテル、テトラヒドロフラン、１，２−ジメト
キシエタン、ジグリム等を溶剤として、水素化リチウム
アルミニウム、水素化ナトリウムアルミニウム等の水素
化アルミニウムのアルカリ金属塩を用いて還元すること
もできる。これらの還元反応は、０℃から用いる溶剤の
沸点までの温度範囲で実施される。A method is used in which a metal catalyst such as platinum, palladium, or nickel is used in a hydrogen atmosphere at normal pressure to diffuse pressure using tetrahydrofuran, ethyl acetate, water, or a mixture thereof as a solvent. The reaction temperature is preferably in the range of 0 to 60°C. The reduction can also be carried out using an alkali metal salt of aluminum hydride such as lithium aluminum hydride or sodium aluminum hydride using ether, tetrahydrofuran, 1,2-dimethoxyethane, diglyme, or the like as a solvent. These reduction reactions are carried out in a temperature range from 0° C. to the boiling point of the solvent used.
つぎに実施例をあげて本発明をさらに詳しく説明するが
、本発明はかかる実施例のみに限定されるものではない
。Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.
実施例１
（Ｒ） −１−メチル−３−フェニルプロピルアジドの
製造
（Ｓ）−１−メチル−３−フェニルプロピル−ｐ−トル
エンスルホネート ８．０４ ｇ（１０ｍｍｏｌ）〔〔
α〕 ±３．６２°（ｃ＝１．０５．ベンゼン）、９１
％ｅ、ｅ、 ］ をジメチルスルホキシド２０ｍＪに
溶解し、４０℃で撹拌しなからＮａＮ３ １．３０Ｂ（
２ｏｍｍｏｌ）を−度に加え２時間反応させた。Example 1 (R) Production of -1-methyl-3-phenylpropyl azide (S) -1-methyl-3-phenylpropyl-p-toluenesulfonate 8.04 g (10 mmol) [[
α] ±3.62° (c=1.05.benzene), 91
%e, e,] was dissolved in 20 mJ of dimethyl sulfoxide, stirred at 40°C, and then dissolved in 1.30 B of NaN3 (
2 ommol) was added at once and reacted for 2 hours.
ついで反応液に水１００ｍＪを加え、生成物を酢酸エチ
ルｓｏｍｇで２回抽出し、有機層を飽和食塩水５０ｍｆ
、水５０ｍ１で洗浄、無水硫酸ナトリウムて乾燥後、有
機溶剤を減圧留去すると、オイル状（７） （Ｒ） −
１−メチル−３−フェニルプロピルアジド １．７０ｇ
（９，７ｍｍｏｌ）、収率９７％、〔ａ〕２５−６６．
０°（Ｃｍ１．０４．クロロホルム）が得られた。Then, 100 mJ of water was added to the reaction solution, the product was extracted twice with ethyl acetate, and the organic layer was dissolved in 50 mf of saturated brine.
After washing with 50 ml of water and drying over anhydrous sodium sulfate, the organic solvent was distilled off under reduced pressure to obtain an oil (7) (R) -
1-methyl-3-phenylpropyl azide 1.70g
(9.7 mmol), yield 97%, [a]25-66.
0° (Cm 1.04.chloroform) was obtained.
元素分析値（Ｃ１０Ｆ１１３ Ｎ３として）計算値（％
） Ｃ：６８．５４ Ｈニア、４８ Ｎ：２３．
９８測定値（％） Ｃ：６８．２４ Ｈニア、５４
Ｎ：２３．９０’Ｈ−ＮＭＲ（９０ＭＨｚ、ＣＤＣ
ｌ５）δｐｐｍ１．１０ （３Ｈ，ｄ、 ＣＨａ ）、
１．７７ （２Ｈ，ｑ、 ＣＨ２）、２．７０ （２）
ｆ、 ｔ、 ＣＨ２）、３．４０ （ＩＨ，ｍ、 ＣＨ
）、７．２３ （５Ｈ，３％Ｃ６Ｈ５）
ｎｅａｔ −１
νｍａｘ Ｃｍ ２９１８．２１０４．１６０５．
１４９８．１４５５．１２５４．
１１２５．１０３５．７４５、
実施例２
（Ｓ：１−１−、’ｌチル・−３−フェニルフロヒルア
ジドの製造
（Ｒ１）−１−メチル−３−フェニルプロピル−ｐ−ト
ルエ：ｚ７．ルホネ−ドア、６０ ｇ （２５ｍｍｏｌ
）〔〔α’：］ −１，８８°（ｅ＝６．０８、ベン
ゼン）、６８％ｅ、ｅ、 〕を〕Ｎ、Ｎ−ジメ千ルホル
ムアミド３０ｍに溶解し、ＮａＮ３ ２．２８ｊ；ｌ（
３５ｍｍｏｌ）を加え、室温下１５時間反応させた。つ
いて実施例１と同様の後処理を行なってオイル状の（Ｓ
）−１−１チル−３−フェニルプロピルアジド４．２０
、Ｓｌ＋（２４ｎ１ｍ０１）、収率９６％、Ｃａ１ｌＤ
＋５２．８゜（ｃ ＝ １．０３ 、 ＣＨＣＩｇ）を
得た。Elemental analysis value (as C10F113 N3) Calculated value (%
) C: 68.54 H near, 48 N: 23.
98 Measured value (%) C: 68.24 H near, 54
N: 23.90'H-NMR (90MHz, CDC
l5) δppm1.10 (3H, d, CHa),
1.77 (2H, q, CH2), 2.70 (2)
f, t, CH2), 3.40 (IH, m, CH
), 7.23 (5H, 3%C6H5) neat −1 νmax Cm 2918.2104.1605.
1498.1455.1254. 1125.1035.745, Example 2 (S: Preparation of 1-1-,'l-3-phenylfurohyl azide (R1)-1-methyl-3-phenylpropyl-p-toluene: z7. - door, 60 g (25 mmol
) [[α':] −1,88° (e = 6.08, benzene), 68% e, e, ] was dissolved in 30 m of N,N-dimethylformamide, and NaN3 2.28j; l (
35 mmol) was added thereto, and the mixture was reacted at room temperature for 15 hours. Then, the same post-treatment as in Example 1 was carried out to obtain an oily (S
)-1-1 thyl-3-phenylpropyl azide 4.20
, Sl+ (24n1m01), yield 96%, Ca1ID
+52.8° (c = 1.03, CHCIg) was obtained.
元素分析値（ＣＩＯＩ１３ Ｎ３ としで）計算値（
％） Ｃ：６８．５４ Ｈニア、４８ Ｎ：２３゜９
８測定値（％） Ｃ：６８．１２ Ｈニア、８４ Ｎ
：２１８８１１Ｉ−ＮＭＲ（９０ＭＨｚ、ＣＤ０１３
）δｐｐｍ１．１０（３ＩＩ、ｄ、ＣＮ（ａ）、１．７
７ （２ＩＮ、 ｑ、 ＣＨ２）、２．７０（２■（、
ｔ、ｅ■（２）、３．４０ （Ｌ Ｈ，ｍ、 ＣＨ）、
７−２３ （５ＩＩ ＝＝ ｓ ｓ Ｇ ６ ＩＮ
５ ）ｎｅａｊ −１２ｇ１ｇ、２１０４．１６０
５、ｖ ｍａｘ ｃｒｎ
１４９８．１４５５．１２５４．
１１２５．１０３５．７４５、
実施例３
（Ｒ） −１−メチル−３−フェニルプロピルアミンの
製造
実施例１で得られた（Ｒ）−１−メチル−３−フェニル
フロヒルアジド１−５８／ （９，０ｍ ｍｏｌ）のメ
タノール溶液（２０ｍｌ）に５％Ｐｄ−０５００ｍ、９
を加え、水素ガス（常圧）雰囲気下、４０℃で８時間反
応させた。反応混合物を渥過し、Ｐｄ−Ｃをメタノ・−
ルで洗浄後、ｐ液と洗浄液を減圧濃縮するとオイルが得
られた。これを減圧下（１４ｍｍｌ−１，；ｒ） １
０１〜１０２℃で蒸留することにより（几）−１−メチ
ル−３−フェニルプロピルアミン １．３１！９（７，
５ｍｍｏｌ）収率８３％、〔ａ：ｌＤ −１０，２°（
ｎｅａｔ） カ得らレタ。Elemental analysis value (CIOI13 N3 Toshide) calculated value (
%) C: 68.54 H near, 48 N: 23°9
8 Measured value (%) C: 68.12 H near, 84 N
:218811I-NMR (90MHz, CD013
) δppm1.10 (3II, d, CN(a), 1.7
7 (2IN, q, CH2), 2.70 (2■(,
t, e (2), 3.40 (L H, m, CH),
7-23 (5II == s s G 6 IN
5) neaj -12g1g, 2104.160
5, v max crn 1498.1455.1254. 1125.1035.745, Example 3 Production of (R)-1-methyl-3-phenylpropylamine (R)-1-methyl-3-phenylfurohyl azide 1-58/ (9 , 0 mmol) in methanol solution (20 ml) of 5% Pd-0500m, 9
was added thereto, and the mixture was reacted at 40° C. for 8 hours under a hydrogen gas (atmospheric pressure) atmosphere. The reaction mixture was filtered to remove Pd-C from methano-
After washing with a vacuum cleaner, the p liquid and washing liquid were concentrated under reduced pressure to obtain an oil. This was under reduced pressure (14 mml-1,; r) 1
By distilling at 01-102°C, (几)-1-methyl-3-phenylpropylamine 1.31!9 (7,
5 mmol) yield 83%, [a: ID −10,2°(
neat) Let's get it.
’Ｈ−ＮＭＲ（９０ＭＨｚ 、ＣＤ０１３）δｐｐｍ１
．０８（３）ｉ、ｄ％ＣＩ（８）、１．５０（２Ｈ１Ｓ
、Ｎｌｌ２）、１．６７ （２Ｈ，Ｑ、 ＣｌＩ２ ）
、２．６５ （２Ｌ ｔ、 ＣＨ２）、２．９０（Ｌ
Ｈｌｍ、Ｃｕ）、７．２０ （５Ｈ，Ｓ、Ｃ６Ｈ３）（
ＩｉＬ） −１−メチル−３−フェニルプロピルアミン
をモツシャー試薬により（→Ｍ、 Ｔ Ｐ Ａアミド化
〔ジャーナル・オブ・オーガニック・ケミストリー、２
４巻、２５４３頁（１９６９年）〕シた後、日本分光製
Ｆｉｎｅｐａｋ ＳＩＬ （４８カラム（展開溶剤ニメ
タノール／水＝ｉ、、’ｉｃ容積比））により、ジアス
テレオマーの分析を行なったところ９２％ｅ、ｅ、と判
明した。'H-NMR (90MHz, CD013) δppm1
．． 08(3)i, d%CI(8), 1.50(2H1S
, Nll2), 1.67 (2H,Q, ClI2)
, 2.65 (2L t, CH2), 2.90 (L
Hlm, Cu), 7.20 (5H, S, C6H3) (
IiL) -1-Methyl-3-phenylpropylamine was converted into (→M, TPA amidation [Journal of Organic Chemistry, 2
4, p. 2543 (1969)], diastereomers were analyzed using Finepak SIL (48 columns (developing solvent nimethanol/water = i, 'ic volume ratio) manufactured by JASCO Corporation). It turned out to be 92% e, e.
実施例４
（Ｓ） −１−メチル−３−フェニルプロピルアミンの
製造
実施例２て得られた（Ｓ） −１−メチル−３−フェニ
ルプロピルアジド４．００ ｇ （２３ｍｍｏｌ）のメ
タノール溶液（３０ｍｌ ）に５％ＰｄＰｄ−Ｃ５０Ｏ
を加え、オートクレーブ中、水素ガス（３に９／ｗ２）
雰囲気下５０℃で５時間反応させた。ついで実施例３と
同様の後処理を行ない、蒸留精製することにより （Ｓ
） −１−メチル−３−フェニルプロピルアミン ２．
９８，９ （２０ｍ ｎｏｌ）、収率８７％、Ｃα〕”
＋ ６．９２°（ｎｅａ ｔ ） ヲ’ｇｇ ７’、
：。 これを（＋）ＭＴＰＡアミド化し、液クロ分析を
行なった結果、６９％ｅ、 ｅ、であった。Example 4 Production of (S)-1-methyl-3-phenylpropylamine Methanol solution (30 ml) of 4.00 g (23 mmol) of (S)-1-methyl-3-phenylpropyl azide obtained in Example 2 5% PdPd-C50O
and hydrogen gas (3 to 9/w2) in an autoclave.
The reaction was carried out at 50° C. for 5 hours in an atmosphere. Then, by performing the same post-treatment as in Example 3 and purifying by distillation, (S
) -1-Methyl-3-phenylpropylamine 2.
98,9 (20 m nol), yield 87%, Cα]”
+6.92°(neat) wo'gg 7',
:. This was amidated with (+)MTPA, and liquid chromatography analysis revealed that it was 69% e.
実施例５
（Ｒ） −１−メチル−３−フェニルプロピルアミンの
製造
（Ｓ） −１−メチル−３−フェニルプロピル−メタン
スルホネート ２．２８．９ （１０ｍ ｍｏｌ）〔〔
α］２５ ＋６．４４°（ｃ＝２．０５、ベンゼン）、
９１％ｅ、ｅ、］を実施例１と同様にアジド化させたと
こ口ＯＬ） −１−メチル−３−フェニルプロピルアジ
ド１．６２１ （９，３ｍｍｏり、収率９３％、〔α］
２５−６５．８°（Ｃ＝１．ＯＯ、クロロホルム）が得
られた。ついで実施例３と同様な方法で（Ｒ）−１−メ
チル−３−フェニルプロピルアジド１．５０ 、ｊｉ！
（８，６ｍ ｍｏｌ）の迎元を行ナイ、（Ｒ）−■−
メチノＬ／−３−フェニルプロピルアミン １．０４１
！；ｉ’（７，□ｍｍｏｌ）、収率８１％、［α：］
−１１，０゜（ｎｅａｔ）、９】％ｅ、ｅ、が得られ
た。Example 5 (R) Production of -1-methyl-3-phenylpropylamine (S) -1-methyl-3-phenylpropyl-methanesulfonate 2.28.9 (10 mmol) [[
α]25 +6.44° (c=2.05, benzene),
91% e, e,] was azidized in the same manner as in Example 1) -1-methyl-3-phenylpropyl azide 1.621 (9.3 mmol, yield 93%, [α]
25-65.8° (C=1.OO, chloroform) was obtained. Then, in the same manner as in Example 3, (R)-1-methyl-3-phenylpropyl azide was added at 1.50, ji!
(8.6m mol), (R) -■-
Methino L/-3-phenylpropylamine 1.041
! ;i'(7,□mmol), yield 81%, [α:]
−11,0° (neat), 9%e, e, was obtained.
実施例６
（ｓ） −ｉ−メチル−３−フェニルプロピルアミンの
製造
（Ｒ，） −１−メチル−３−フェニルプロピル−メタ
ンスルホネート ６８４ｍｇ（３ｍｍｏり［［α：ｌ”
−３，７５°（Ｃ＝１．０７、Ｃ１，ＩＣ１ｇ ）、６
８％ｅ、ｅ、 ）を実施例２と同様にアジド化し、（Ｓ
） −１−メチル−３−フェニルプロピルアジド ４５
５ｍ、９（２，６ｍｍｏｌ）、収率８７％、Ｃα〕２６
−１−４０．０８（Ｃ＝１．０９、ＣｌＩＣ１ａ）が得
られた。ついで実施例３と同様な方法で（Ｓ）−１−メ
チル−３−フェニルプロピルアジド ３５０ｍ、！９
（２，０ｍｍｏｌ）の血元を行ない（Ｓ） −１−メチ
ル−３−フェニルプロピルアミ” ２８８ｍ、９（１
，９ｍｍｏｉ）、収率９５％、６７％ｅ、 ｅ、を得た
つ
実施例７
（Ｓ） −ｔ−メチル−３−フェニルプロピルアミンの
製造
実施例２で得られた（Ｓ） −１−メチル−３−フェニ
ルプロピルアジド ５００ ｍｌ！ （２，９ｍ ｍｏ
ｌ）を５ｍＪのエーテルに溶解し、室温下、水素化アル
ミニウム’）＋’）ム５７ｍ、９（１，５ｍｍ０１）の
エーテル溶液を３０分にわたり滴−Ｆｔ〜た。さらに１
時間撹拌後、水１０ｍ１を加えて反応を停止［７，２０
ｍｆｃＤｉト酸エチルで２回抽出し、有機層を飽和食塩
水ＩＱｍＪ、 水１０ｍＪで洗浄、無水硫酸すｌ−Ｉ
Ｊウムて乾燥後、有機溶剤を減圧留去した。Example 6 (s) Production of -i-methyl-3-phenylpropylamine (R,) -1-Methyl-3-phenylpropyl-methanesulfonate 684 mg (3 mmol [[α:l”
-3,75° (C=1.07, C1, IC1g), 6
8%e, e, ) was converted into azide in the same manner as in Example 2, and (S
) -1-methyl-3-phenylpropyl azide 45
5m, 9 (2.6 mmol), yield 87%, Cα]26
-1-40.08 (C=1.09, ClIC1a) was obtained. Then, in the same manner as in Example 3, 350 m of (S)-1-methyl-3-phenylpropyl azide,! 9
(2,0 mmol) of blood sample (S)-1-methyl-3-phenylpropylamine” 288m, 9(1
Example 7 Production of (S)-t-methyl-3-phenylpropylamine (S)-1-methyl- obtained in Example 2 3-phenylpropyl azide 500 ml! (2,9m mo
1) was dissolved in 5 mJ of ether, and an ether solution of aluminum hydride ')+') 57m, 9 (1,5 mm 01) was added dropwise over 30 minutes at room temperature. 1 more
After stirring for an hour, 10 ml of water was added to stop the reaction [7,20
Extracted twice with mfcDi ethyl torate, washed the organic layer with saturated brine IQmJ, water 10mJ, anhydrous sulfuric acid l-I
After drying under vacuum, the organic solvent was distilled off under reduced pressure.
さらに減圧下（１４ｍｍＨ７） １００°〜１１７℃
で蒸留することによ、？（８）−１−メチル−３−フェ
ニルプロピルアミン ３５８ ｍ、９ （２，４ｍｍｏ
ｌ）、８３％収率、７０％ｅ、 ｅ、が得られた、。Further under reduced pressure (14mmH7) 100° to 117°C
By distilling it? (8)-1-Methyl-3-phenylpropylamine 358 m, 9 (2,4 mmo
l), 83% yield, 70% e, e, was obtained.
実施例８
（几）−１−メチル−３−フェニルプロピルアジドの製
造
（Ｓ）−１−メチル−３−フェニルプロピルエタンスル
ホネート １．９６９ （８，１ｍｍｏｌ） ［α］”
”＋４．１２°（Ｃ＝２．０９、ベンゼン）〕を実施例
２と同様にＮａＮａ １．０５．！ｉ’ （１６ｒｎ
ｍｏｌ） と反応、後処理を行ない、（Ｒ，） −１
−メチル−３−フェニルプロピルアジド １．８７ ｊ
９ （７，８ｍｍｏｌ）、収率９６９６、〔α〕 −６
０，９°（ｃ＝１．０２、クロロホルム）を得た。Example 8 Production of (几)-1-methyl-3-phenylpropylazide (S)-1-methyl-3-phenylpropylethanesulfonate 1.969 (8.1 mmol) [α]”
"+4.12° (C=2.09, benzene)] in the same manner as in Example 2, NaNa 1.05.!i' (16rn
mol) and post-treatment, (R,) -1
-Methyl-3-phenylpropyl azide 1.87 j
9 (7.8 mmol), yield 9696, [α] -6
0.9° (c=1.02, chloroform) was obtained.
Claims (5)
１−メチル−３−フェニルプロピルアジド。(1) Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) Optically active 1-methyl-3-phenylpropyl azide represented by (in the formula, * represents a lower enzymatic carbon).
、ｐ−メチルフェニルあるいはベンジル基を表わす）で
表わされる光学活性スルホニルオキシ化合物と、アジ化
水素のアルカリ金属塩と反応させることを特徴とする、
式（ I ） ▲数式、化学式、表等があります▼（ I ） （式中、＊は上記と同じ）で表わされる光学活性１−メ
チル−３−フェニルプロピルアジドの製造法。(2) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) (In the formula, * represents a lower atom carbon, R represents methyl, ethyl, phenyl, p-methylphenyl, or benzyl group) characterized by reacting the optically active sulfonyloxy compound represented by the formula with an alkali metal salt of hydrogen azide,
Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) A method for producing optically active 1-methyl-3-phenylpropyl azide represented by (in the formula, * is the same as above).
ルである特許請求の範囲第２項記載の製造法。(3) The production method according to claim 2, wherein R is methyl, ethyl, or p-methylphenyl.
ェニルあるいはベンジル基、＊は不斉炭素を表わす）で
表わされる光学活性スルホニルオキシ化合物を、アジ化
水素のアルカリ金属塩と反応させ、光学活性１−メチル
−３−フェニルプロピルアジドを得、次いでこの生成物
を還元反応に付することを特徴とする光学活性１−メチ
ル−３−フェニルプロピルアミンの製造法。(4) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) (In the formula, R is methyl, ethyl, phenyl, p-methylphenyl or benzyl group, * represents an asymmetric carbon) An optical method characterized by reacting the optically active sulfonyloxy compound expressed with an alkali metal salt of hydrogen azide to obtain optically active 1-methyl-3-phenylpropyl azide, and then subjecting this product to a reduction reaction. Method for producing active 1-methyl-3-phenylpropylamine.
である特許請求の範囲第４項記載の製造法。(5) The production method according to claim 4, wherein R is methyl, ethyl or p-methylphenyl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19876786A JPS6354351A (en) | 1986-08-25 | 1986-08-25 | Optically active 1-methyl-3-phenylpropylazide and production of optically active amine using said compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19876786A JPS6354351A (en) | 1986-08-25 | 1986-08-25 | Optically active 1-methyl-3-phenylpropylazide and production of optically active amine using said compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6354351A true JPS6354351A (en) | 1988-03-08 |
Family
ID=16396593
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19876786A Pending JPS6354351A (en) | 1986-08-25 | 1986-08-25 | Optically active 1-methyl-3-phenylpropylazide and production of optically active amine using said compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6354351A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04234832A (en) * | 1990-03-08 | 1992-08-24 | Fujisawa Pharmaceut Co Ltd | New substituted amine compound and its production |
| JP2002179628A (en) * | 2000-12-08 | 2002-06-26 | Daiichi Fine Chemical Co Ltd | Method for producing optically active diamine derivative |
| JP2009023933A (en) * | 2007-07-19 | 2009-02-05 | National Institute Of Advanced Industrial & Technology | Nitrogen-containing organic silicon compound |
| US8603567B2 (en) | 2002-10-30 | 2013-12-10 | Suntory Holdings Limited | Method of manufacturing plant finished product |
-
1986
- 1986-08-25 JP JP19876786A patent/JPS6354351A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04234832A (en) * | 1990-03-08 | 1992-08-24 | Fujisawa Pharmaceut Co Ltd | New substituted amine compound and its production |
| JP2002179628A (en) * | 2000-12-08 | 2002-06-26 | Daiichi Fine Chemical Co Ltd | Method for producing optically active diamine derivative |
| US8603567B2 (en) | 2002-10-30 | 2013-12-10 | Suntory Holdings Limited | Method of manufacturing plant finished product |
| JP2009023933A (en) * | 2007-07-19 | 2009-02-05 | National Institute Of Advanced Industrial & Technology | Nitrogen-containing organic silicon compound |
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