CS224979B1 - The production of pentacyclic lactam-esters - Google Patents

The production of pentacyclic lactam-esters Download PDF

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Publication number
CS224979B1
CS224979B1 CS571882A CS571882A CS224979B1 CS 224979 B1 CS224979 B1 CS 224979B1 CS 571882 A CS571882 A CS 571882A CS 571882 A CS571882 A CS 571882A CS 224979 B1 CS224979 B1 CS 224979B1
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Czechoslovakia
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formula
esters
pentacyclic
lactam
production
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CS571882A
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Czech (cs)
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Josef Ing Csc Hajicek
Jan Dr Ing Csc Trojanek
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Hajicek Josef
Jan Dr Ing Csc Trojanek
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Priority to CS571882A priority Critical patent/CS224979B1/en
Publication of CS224979B1 publication Critical patent/CS224979B1/en

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Description

Vynález se týká způsobu výroby pentacyklických laktam-The present invention relates to a process for the preparation of pentacyclic lactams.

ve kterém R značí alkyl s 1 až 4 atomy uhlíku a n je 2 nebo 3. Sloučeniny vzorce I jsou vesměs nové a představují důležité me ziprodukty při výrobě biologicky aktivních látek.wherein R is C1-C4 alkyl and n is 2 or 3. The compounds of formula I are all novel and are important intermediates in the production of biologically active substances.

Podstata způsobu výroby podle vynálezu spočívá v tom, že se diestery 2-oxo-cykloalkan-1,3-dipropionových kyselin Obecné ho vzorce II,The process according to the invention is characterized in that the diesters of 2-oxo-cycloalkane-1,3-dipropionic acids of the general formula II,

ROOCROOC

COOR (II) ve kterém R i n mají shora uvedený význam, zahřívají k varu s tryptaminem vzorce IIICOOR (II) wherein R 1 and n are as defined above, are heated to boiling with the tryptamine of formula III

(III) ve výševroucím organickém rozpouštědle, jako např. v xylenu, diglymu, difenyletheru nebo chlorbenzenu.(III) in a high boiling organic solvent such as xylene, diglyme, diphenyl ether or chlorobenzene.

Následující příklady ilustrují, avšak nikterak neomezují obecnost způsobu výroby podle vynálezu.The following examples illustrate but do not limit the generality of the inventive process.

PřikladlHe did

224 979224 979

Směs 16^22 g (60 mmol) dimethyl-2-oxocyklohexan-1,3-dipropionátu (II ·,' R = CH^, n = 3) a 9^61 g (60 mmol) tryptaminu (III) se zahřívá k varu ve 150 ml silenu 11^5 h a koncentruje se ve vakuu vodní vývěvy. Zbytek se rozpustí v 500 ml chloroformu a promyje se postupně 100 ml 3% kyseliny chlorovodíkové, 100 ml vody a 50 ml solanky. Organická fáze se vysuší bezvodým síranem hořečnatým a zahustí se za sníženého tlaku. Odparek se chromatografuje na 130 g silikagelu. Odpařením benzen-chloroformových eluátů (3:1 až 1:1) na rotační vakuové odparce a následující krystalisací ze směsi methanolu a ethyl-acetátu se získá 7^78 g (34^1 %) laktamesteru vzorce I (R = GH^, n = 3). Teplota tání leží v rozmezí 148 až 149r5 °C.A mixture of 16 - 22 g (60 mmol) of dimethyl 2-oxocyclohexane-1,3-dipropionate (II, R = CH3, n = 3) and 9 - 61 g (60 mmol) of tryptamine (III) is heated to boiling in 150 ml of 11- 5 h silene and concentrated in a water pump vacuum. The residue was dissolved in 500 ml of chloroform and washed successively with 100 ml of 3% hydrochloric acid, 100 ml of water and 50 ml of brine. The organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is chromatographed on 130 g of silica gel. Evaporation of the benzene-chloroform eluates (3: 1 to 1: 1) on a rotary evaporator followed by crystallization from a mixture of methanol and ethyl acetate gave 7 ^ 78 g (34 1 1%) of the lactamester of formula I (R = GH ^, n). = 3). The melting point ranges from 148 to 149 y 5 ° C.

Příklad 2Example 2

Směs 13^58 g (53 mmol) dimethyl-2-oxocyklopentan~1,3-dipropionátu (II, R = CH^, n = 2), 8^01 g (50 mmol) tryptaminu (III) a 170 ml diglymu se zahřívá k varu 9 h a odpaří se ve vakuu vodní vývěvy. Zbytek se chromatografuje na 115 g silikagelu. Eluáty směsí benzenu a chloroformu 4:1 až 1:1 se spojí a odpaří za sníženého tlaku na rotační odparce. Odparek se krystaluje z methanolu a získá se 8^16 g laktam-esteru vzorce I (R = CHp n = 2) s teplotou tání 124 až 127 °C · Výtěžek odpovídá 44^5 %· Příklad 3A mixture of 13-58 g (53 mmol) of dimethyl 2-oxocyclopentane-1,3-dipropionate (II, R = CH3, n = 2), 8.01 g (50 mmol) of tryptamine (III) and 170 ml of diglyme is added. Heat to boiling 9 h and evaporate in a water pump vacuum. The residue is chromatographed on 115 g of silica gel. The eluates of benzene / chloroform 4: 1 to 1: 1 were combined and evaporated under reduced pressure on a rotary evaporator. The residue is crystallized from methanol to give 8 16 g of the lactam ester of formula I (R = CHp n = 2), m.p. 124-127 ° C.

Postupem podle příkladu 2 se získá z dibutyl-2-oxocyklopentan-1,3-dipropionátu (II, R = CH3CH2CH2CH2, n = 2) 19,7 % laktamesteru vzorce I (R = CH3CH2CH2GH2, n = 2) v podobě transparentního skla.Following the procedure of Example 2, 19.7% of the lactamester of formula I (R = CH 3 CH 2 ) was obtained from dibutyl 2-oxocyclopentane-1,3-dipropionate (II, R = CH 3 CH 2 CH 2 CH 2 , n = 2). CH 2 GH 2 , n = 2) in the form of transparent glass.

Příklad 4Example 4

Postupem podle příkladu 1 se získá z dibutyl-2-oxocyklohexan1,3-dipropionátu (II, R = GH^CHgCHgCHg, n - 3) 22^8 % laktam-esteru vzorce I (R = CH^CHgCHgCHg, n = 3) v podobě transparentního skla.Following the procedure of Example 1, 22% -8% of the lactam ester of formula I (R = CH3CH3CHgCHg, n = 3) is obtained from dibutyl 2-oxocyclohexane-1,3-dipropionate (II, R = GH2CH2CHgCHg, n-3). form of transparent glass.

Směs 2,7 g (10 mmol) dimethyl-2-oxocyklohexan-1,3-dipropio nátu (II, R = CHp n = 3), 1,6 g (10 mmol)tryptaminu (III) a 50 ml chlorbenzenu se zahřívá 25 h k varu a zpracuje se podle příkladu 2. Získá se 30,7 % (1,17 g) laktam-esteru vzorce I (R = CH^, n = 3) s teplotou tání 148,5 až 149,5 °C.A mixture of 2.7 g (10 mmol) of dimethyl 2-oxocyclohexane-1,3-dipropionate (II, R = CHp n = 3), 1.6 g (10 mmol) of tryptamine (III) and 50 ml of chlorobenzene is heated. It was boiled for 25 h and worked up as in Example 2. 30.7% (1.17 g) of the lactam ester of formula I (R = CH 2, n = 3) were obtained, m.p. 148.5-149.5 ° C.

Claims (1)

Způsob výroby pentacyklických laktam-esterů obecného vzor224 979 ce I, (X) ve kterém R značí alkyl s 1 až 4 atomy uhlíku a n je 2 nebo 3, vyznačený tím, že se estery 2-oxocykloalkan-1,3-dipropionových kyselin obecného vzorce II,A process for the preparation of pentacyclic lactam esters of formula (24) 79 (I), (X) wherein R is C 1 -C 4 alkyl and n is 2 or 3, characterized in that the esters of 2-oxocycloalkane-1,3-dipropionic acids of the formula II, ROOC ROOC COOR (II) ve kterém R i n mají shora uvedený význam, zahřívají k varu s tryptaminem vzorce III (III) ve výševroucím organickém rozpouštědle, jako např. v xylenu, diglymu, difenyletheru nebo chlorbenzenu.COOR (II) wherein R 1 and n are as defined above, are heated to boiling with tryptamine of formula III (III) in a high boiling organic solvent such as xylene, diglyme, diphenyl ether or chlorobenzene.
CS571882A 1982-07-29 1982-07-29 The production of pentacyclic lactam-esters CS224979B1 (en)

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