JPS6411022B2 - - Google Patents
Info
- Publication number
- JPS6411022B2 JPS6411022B2 JP56048285A JP4828581A JPS6411022B2 JP S6411022 B2 JPS6411022 B2 JP S6411022B2 JP 56048285 A JP56048285 A JP 56048285A JP 4828581 A JP4828581 A JP 4828581A JP S6411022 B2 JPS6411022 B2 JP S6411022B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- solvent
- reaction
- spiro
- cyclopropane
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 9
- 150000003413 spiro compounds Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- 238000000921 elemental analysis Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- TVAWDXKGAUYNRP-UHFFFAOYSA-N 7-acetylspiro[1-benzofuran-2,1'-cyclopropane]-3-one Chemical compound O1C=2C(C(=O)C)=CC=CC=2C(=O)C21CC2 TVAWDXKGAUYNRP-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 208000023652 chronic gastritis Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- CONFKPNJMSFBNF-UHFFFAOYSA-N methyl 3-acetyl-2-(2-oxooxolan-3-yl)oxybenzoate Chemical compound COC(=O)C1=CC=CC(C(C)=O)=C1OC1C(=O)OCC1 CONFKPNJMSFBNF-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- TVNIWLZLXRXNAJ-UHFFFAOYSA-N spiro[1-benzofuran-2,1'-cyclopropane]-3-one Chemical compound O=C1C2=CC=CC=C2OC11CC1 TVNIWLZLXRXNAJ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LFJJGHGXHXXDFT-UHFFFAOYSA-N 3-bromooxolan-2-one Chemical compound BrC1CCOC1=O LFJJGHGXHXXDFT-UHFFFAOYSA-N 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- -1 etc. Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000457 gamma-lactone group Chemical group 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- APYIKEJEROJJIK-UHFFFAOYSA-N methyl 3-acetyl-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=CC(C(C)=O)=C1O APYIKEJEROJJIK-UHFFFAOYSA-N 0.000 description 1
- YXYZYOZJUSGSEI-UHFFFAOYSA-N methyl 5-acetyl-2-(2-oxooxolan-3-yl)oxybenzoate Chemical compound COC(=O)C1=CC(C(C)=O)=CC=C1OC1C(=O)OCC1 YXYZYOZJUSGSEI-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は医薬として有用な新規スピロ化合物お
よびその製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel spiro compounds useful as pharmaceuticals and methods for producing the same.
さらに詳しくは、本発明は一般式
で表わされる新規スピロ化合物およびその製造方
法に関するものである。 More specifically, the present invention relates to the general formula This invention relates to a novel spiro compound represented by and a method for producing the same.
上記式()に関し、1−ヒドロキシエチル基
はベンゼン環上の置換可能な位置のいずれに置換
されていてもよく、とりわけ5位または7位に置
換されていることが好ましい。 Regarding the above formula (), the 1-hydroxyethyl group may be substituted at any substitutable position on the benzene ring, and is preferably substituted at the 5th or 7th position.
本発明のスピロ化合物()は、たとえば式
で表わされる化合物を還元することにより製造で
きる。本反応は適当な溶媒中で行われ、かかる溶
媒としては反応を阻害しない限りどのようなもの
でもよいが、通常エーテル、テトラヒドロフラ
ン、ジオキサン、ジメトキシエタン、塩化メチレ
ン、ピリジン、イソプロピルアルコールなどまた
はこれらの混合溶媒が用いられる。還元反応にお
ける還元剤としては、たとえば水素化ホウ素ナト
リウム、水素化ホウ素カリウムなどの金属水素化
ホウ素化合物が好都合に用いられる。反応温度と
しては、通常約−70〜+40℃程度、とりわけ約−
15〜+20℃程度が好都合であるが、3位カルボニ
ル基の還元を抑えるためおよび反応速度調節の目
的でより低温または高温で反応させてもよい。 The spiro compound () of the present invention may be, for example, a compound of the formula It can be produced by reducing the compound represented by This reaction is carried out in a suitable solvent, and any solvent may be used as long as it does not inhibit the reaction, but usually ether, tetrahydrofuran, dioxane, dimethoxyethane, methylene chloride, pyridine, isopropyl alcohol, etc., or a mixture thereof. A solvent is used. As the reducing agent in the reduction reaction, metal borohydride compounds such as sodium borohydride and potassium borohydride are conveniently used. The reaction temperature is usually about -70 to +40℃, especially about -
A temperature of about 15 to +20°C is convenient, but the reaction may be carried out at a lower or higher temperature for the purpose of suppressing the reduction of the carbonyl group at the 3-position and controlling the reaction rate.
かくして製造された目的化合物()は通常の
分離精製手段(例、蒸留、クロマトグラフイー)
により反応混合物から単離精製することができ
る。化合物()には不斉炭素原子に基づく光学
異性体が存在するが、これらも当然本発明の範囲
に包含されるものである。 The target compound () produced in this way can be purified by ordinary separation and purification means (e.g. distillation, chromatography).
It can be isolated and purified from the reaction mixture by . Compound () has optical isomers based on asymmetric carbon atoms, and these are naturally included in the scope of the present invention.
本発明のスピロ化合物()は、たとえば哺乳
動物(例、ヒト、ラツト、マウス、モルモツト、
イヌ、ブタ)に対して胃液分泌抑制作用、消炎作
用、鎮痛作用などを示し、たとえば胃・十二指腸
潰瘍、急慢性胃炎、腰痛、関節炎などの疾病に対
する抗潰瘍剤、消炎剤、鎮痛剤などとして有用で
ある。たとえば、5位に1−ヒドロキシエチル基
を有するスピロ化合物()は、ロベール
(Robert)らの方法〔ガストロエンテロロギー
(Gastroenterology)、77、433(1979)〕による試
験でラツトにおける胃粘膜損傷を50mg/Kgで強力
に抑制し、かつ低毒性である。上記の医薬として
用いる場合、化合物()をそのままもしくは自
体公知の賦形剤等と共に錠剤、散剤、カプセル
剤、注射剤、坐剤などの適宜の剤形として経口的
または非経口的に安全に投与することができる。
投与量は投与対象、症状、投与ルート等によつて
も異なるが、通常成人の胃・十二指腸潰瘍や急慢
性胃炎に対する治療剤として経口投与する場合、
化合物()を1回量約1〜20mg/Kg体重程度、
1日約1〜3回程度投与するのが好都合である。 The spiro compound () of the present invention can be used, for example, in mammals (e.g., humans, rats, mice, guinea pigs,
It has suppressive effects on gastric juice secretion, anti-inflammatory effects, and analgesic effects on dogs and pigs, and is useful as an anti-ulcer agent, anti-inflammatory agent, and analgesic for diseases such as gastric/duodenal ulcers, acute chronic gastritis, low back pain, and arthritis. It is. For example, a spiro compound (2007) having a 1-hydroxyethyl group at the 5-position caused gastric mucosal damage in rats at 50 mg in a test according to the method of Robert et al. [Gastroenterology, 77 , 433 (1979)]. /Kg, and has low toxicity. When used as the above-mentioned medicine, the compound () can be safely administered orally or parenterally as it is or in an appropriate dosage form such as tablets, powders, capsules, injections, and suppositories with known excipients. can do.
The dosage varies depending on the subject, symptoms, administration route, etc., but when administered orally as a treatment for gastric/duodenal ulcers or acute chronic gastritis in adults,
A single dose of the compound () is approximately 1 to 20 mg/Kg body weight,
It is convenient to administer about 1 to 3 times a day.
なお、本発明化合物()の製造に用いられる
原料化合物()は、たとえば特開昭55−2623号
に記載の方法またはこれに準じて製造することが
できる。 The starting compound () used in the production of the compound () of the present invention can be produced, for example, by the method described in JP-A-55-2623 or in accordance therewith.
以下に本発明を参考例および実施例によりさら
に具体的に説明するが、本発明の範囲がこれらに
限定されるものではない。 The present invention will be explained in more detail below using reference examples and examples, but the scope of the present invention is not limited thereto.
参考例 1
3−アセチルサリチル酸メチルエステル5.8g
および炭酸カリウム10.4gをアセトン200ml中か
きまぜながらα−ブロモ−γ−ブチロラクトン
12.5gを滴下し、ついで反応液を11時間加熱還流
する。不溶物をろ去し、ろ液を減圧下濃縮する。
残留物をシリカゲルクロマトグラフイーに付し、
クロロホルムで溶出してα−〔(6−アセチル−2
−メトキシカルボニルフエニル)オキシ〕−γ−
ブチロラクトンを淡黄色油状物として得る。Reference example 1 3-acetylsalicylic acid methyl ester 5.8g
and α-bromo-γ-butyrolactone while stirring 10.4 g of potassium carbonate in 200 ml of acetone.
12.5 g was added dropwise, and the reaction solution was then heated under reflux for 11 hours. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure.
The residue was subjected to silica gel chromatography,
Elute with chloroform to obtain α-[(6-acetyl-2
-methoxycarbonylphenyl)oxy]-γ-
Butyrolactone is obtained as a pale yellow oil.
赤外吸収スペクトルνfilm naxcm-1:1780(γ−ラク
トン)、1720(COOCH3)、1690(COCH3)
元素分析 C14H14O6
計算値 C60.43;H5.07
実測値 C60.21;H5.02
参考例 2
α−〔(6−アセチル−2−メトキシカルボニル
フエニル)オキシ〕−γ−ブチロラクトン3.5g、
1,8−ジアザビシクロ〔5,4,0〕−7−ウ
ンデセン0.14g、塩化ナトリウム1.1gをN,N
−ジメチルホルムアミド66.5ml中150〜160℃で5
時間かきまぜる。溶媒を減圧下留去し、残留物を
酢酸エチルに溶かす。酢酸エチル溶液を水洗し、
乾燥する。溶媒を減圧下留去し、残留物をシリカ
ゲルクロマトグラフイーに付す。塩化メチレンで
溶出する目的物をクロロホルム−ヘキサンより再
結晶して7−アセチルスピロ〔ベンゾ〔b〕フラ
ン−2(3H)、1′−シクロプロパン〕−3−オンを
無色針状晶として得る。融点114−115℃。 Infrared absorption spectrum ν film nax cm -1 : 1780 (γ-lactone), 1720 (COOCH 3 ), 1690 (COCH 3 ) Elemental analysis C 14 H 14 O 6 Calculated value C60.43; H5.07 Actual value C60. 21; H5.02 Reference example 2 α-[(6-acetyl-2-methoxycarbonylphenyl)oxy]-γ-butyrolactone 3.5 g,
0.14 g of 1,8-diazabicyclo[5,4,0]-7-undecene and 1.1 g of sodium chloride were mixed with N,N
-5 at 150-160°C in 66.5 ml of dimethylformamide
Stir the time. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Wash the ethyl acetate solution with water,
dry. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography. The target product eluted with methylene chloride is recrystallized from chloroform-hexane to obtain 7-acetylspiro[benzo[b]furan-2(3H), 1'-cyclopropane]-3-one as colorless needles. Melting point 114-115℃.
元素分析 C12H10O3
計算値 C71.28;H4.99
実測値 C71.39;H4.96
参考例 3
α−〔(4−アセチル−2−メトキシカルボニル
フエニル)オキシ〕−γ−ブチロラクトン2.8g、
1,8−ジアザビシクロ〔5,4,0〕−7−ウ
ンデセン0.056g、塩化ナトリウム0.6gをN,N
−ジメチルホルムアミド28ml中150〜155℃で4時
間加熱する。溶媒を減圧下留去し、残留物を酢酸
エチルに溶かす。酢酸エチル溶液を水洗し、乾燥
する。溶媒を減圧下留去して得られる残留物をシ
リカゲルクロマトグラフイーに付す。塩化メチレ
ンで溶出する画分をエタノールから再結晶して5
−アセチルスピロ〔ベンゾ〔b〕フラン−2
(3H)、1′−シクロプロパン〕−3−オン1.15gを
無色結晶として得る。融点100−103℃。赤外吸収
スペクトルνKBr naxcm-1:1700、1680(CO、
COCH3)。核磁気共鳴スペクトル(CDCl3)δ:
1.70(4H、q、J=7Hz、CH2)、2.62(3H、s、
COCH3)、7.20(1H、d、J=9Hz、aromat、
H)、8.27、8.30(1H、dd、J=9Hz、aromat.
H)、8.29(1H、d、J=2Hz、aromat.H)
元素分析 C12H10O3
計算値 C71.28;H4.99
実測値 C71.07;H4.82
実施例 1
5−アセチルスピロ〔ベンゾ〔b〕フラン−2
(3H)、1′−シクロプロパン〕−3−オン1gをテ
トラヒドロフラン25mlおよびイソプロピルアルコ
ール3mlの混液に溶かし−50℃でかきまぜなが
ら、水素化ホウ素ナトリウム0.9gを少量ずつ加
える。ついで室温で30分間かきまぜたのち、反応
液を氷水で希釈し、塩化アンモニウム水溶液で中
和する。水溶液を酢酸エチルで抽出する。抽出液
を水洗し、乾燥する。溶媒を留去して得られる残
留物をシリカゲルクロマトグラフイ−に付し、ク
ロロホルムで溶出する。生成物を減圧蒸留に付し
5−(1−ヒドロキシエチル)スピロ〔ベンゾ
〔b〕フラン−2(3H)、1′−シクロプロパン〕−
3−オンを無色油状物として得る。bp110℃(浴
温)(0.05mmHg)
赤外吸収スペクトルνfilm naxcm-1:3350(OH)、
1710(CO)。核磁気共鳴スペクトル(重クロロホ
ルム)δ;1.45(3H、d、J=6Hz、CH3)、1.62
(4H、q、J=3Hz、CH2)、3.33(1H、b、
OH)、4.83(1H、q、J=6Hz、CH)、6.97(1H、
d、J=9Hz、芳香環H)、7.55(2H、m、芳香
環H)
元素分析 C12H12O3
計算値 C70.57;H5.92
実測値 C70.47;H6.05
実施例 2
7−アセチルスピロ〔ベンゾ〔b〕フラン−2
−(3H),1′−シクロプロパン〕−3−オンを実施
例1と同様に反応し、7−(1−ヒドロキシエチ
ル)スピロ〔ベンゾ〔b〕フラン−2(3H),
1′−シクロプロパン〕−3−オンを得る。Elemental analysis C 12 H 10 O 3 Calculated value C71.28; H4.99 Actual value C71.39; H4.96 Reference example 3 α-[(4-acetyl-2-methoxycarbonylphenyl)oxy]-γ-butyrolactone 2.8g,
0.056 g of 1,8-diazabicyclo[5,4,0]-7-undecene and 0.6 g of sodium chloride were mixed with N,N
- Heat in 28 ml of dimethylformamide at 150-155°C for 4 hours. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate. Wash the ethyl acetate solution with water and dry. The solvent is distilled off under reduced pressure and the resulting residue is subjected to silica gel chromatography. The fraction eluted with methylene chloride was recrystallized from ethanol.
-acetylspiro[benzo[b]furan-2
1.15 g of (3H), 1'-cyclopropane]-3-one are obtained as colorless crystals. Melting point 100-103℃. Infrared absorption spectrum ν KBr nax cm - 1: 1700, 1680 (CO,
COCH3 ). Nuclear magnetic resonance spectrum ( CDCl3 ) δ:
1.70 (4H, q, J=7Hz, CH 2 ), 2.62 (3H, s,
COCH 3 ), 7.20 (1H, d, J=9Hz, aromat,
H), 8.27, 8.30 (1H, dd, J=9Hz, aromat.
H), 8.29 (1H, d, J=2Hz, aromat.H) Elemental analysis C 12 H 10 O 3 Calculated value C71.28; H4.99 Actual value C71.07; H4.82 Example 1 5-acetylspiro [benzo[b]furan-2
(3H), 1'-cyclopropane]-3-one is dissolved in a mixture of 25 ml of tetrahydrofuran and 3 ml of isopropyl alcohol, and while stirring at -50°C, 0.9 g of sodium borohydride is added little by little. After stirring at room temperature for 30 minutes, the reaction solution was diluted with ice water and neutralized with an aqueous ammonium chloride solution. Extract the aqueous solution with ethyl acetate. Wash the extract with water and dry. The residue obtained by distilling off the solvent is subjected to silica gel chromatography and eluted with chloroform. The product was subjected to vacuum distillation to give 5-(1-hydroxyethyl)spiro[benzo[b]furan-2(3H),1'-cyclopropane]-
3-one is obtained as a colorless oil. bp110℃ (bath temperature) (0.05mmHg) Infrared absorption spectrum ν film nax cm -1 : 3350 (OH),
1710 (CO). Nuclear magnetic resonance spectrum (deuterochloroform) δ; 1.45 (3H, d, J=6Hz, CH 3 ), 1.62
(4H, q, J = 3Hz, CH 2 ), 3.33 (1H, b,
OH), 4.83 (1H, q, J=6Hz, CH), 6.97 (1H,
d, J=9Hz, aromatic ring H), 7.55 (2H, m, aromatic ring H) Elemental analysis C 12 H 12 O 3 Calculated value C70.57; H5.92 Actual value C70.47; H6.05 Example 2 7-Acetylspiro[benzo[b]furan-2
-(3H),1'-cyclopropane]-3-one was reacted in the same manner as in Example 1, and 7-(1-hydroxyethyl)spiro[benzo[b]furan-2(3H),
1'-cyclopropane]-3-one is obtained.
赤外吸収スペクトルνfilm naxcm-1:3400(OH)、
1700(CO)
元素分析 C12H12O3
計算値 C70.57;H5.92
実測値 C70.36;H5.89 Infrared absorption spectrum ν film nax cm -1 : 3400 (OH),
1700 (CO) Elemental analysis C 12 H 12 O 3 Calculated value C70.57; H5.92 Actual value C70.36; H5.89
Claims (1)
式 で表わされるスピロ化合物の製造方法。[Claims] 1 formula A spiro compound represented by 2 formulas A formula characterized by reducing the compound represented by A method for producing a spiro compound represented by
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/257,317 US4330554A (en) | 1980-04-23 | 1981-04-17 | Spirobenzofuranone compounds |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GR61757A GR66729B (en) | 1979-05-04 | 1980-04-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS56154477A JPS56154477A (en) | 1981-11-30 |
JPS6411022B2 true JPS6411022B2 (en) | 1989-02-23 |
Family
ID=10931869
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP4828581A Granted JPS56154477A (en) | 1980-04-23 | 1981-03-30 | Spiro compound and its preparation |
JP4828681A Pending JPS56154478A (en) | 1977-12-27 | 1981-03-30 | Spiro compound and its preparation |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP4828681A Pending JPS56154478A (en) | 1977-12-27 | 1981-03-30 | Spiro compound and its preparation |
Country Status (1)
Country | Link |
---|---|
JP (2) | JPS56154477A (en) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS552623A (en) * | 1978-06-19 | 1980-01-10 | Takeda Chem Ind Ltd | Spiro compound and its preparation |
JPS5931511A (en) * | 1982-08-14 | 1984-02-20 | 住友電気工業株式会社 | Power cable using metal wire woven tape |
-
1981
- 1981-03-30 JP JP4828581A patent/JPS56154477A/en active Granted
- 1981-03-30 JP JP4828681A patent/JPS56154478A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
JPS56154478A (en) | 1981-11-30 |
JPS56154477A (en) | 1981-11-30 |
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