WO1988000190A1 - Derives optiquement actifs de glycidol - Google Patents

Derives optiquement actifs de glycidol Download PDF

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Publication number
WO1988000190A1
WO1988000190A1 PCT/US1987/001523 US8701523W WO8800190A1 WO 1988000190 A1 WO1988000190 A1 WO 1988000190A1 US 8701523 W US8701523 W US 8701523W WO 8800190 A1 WO8800190 A1 WO 8800190A1
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WO
WIPO (PCT)
Prior art keywords
compound
purified
produced
formula
glycidyl
Prior art date
Application number
PCT/US1987/001523
Other languages
English (en)
Inventor
Karl Barry Sharpless
Tetsuo H. Onami
Original Assignee
Massachusetts Institute Of Technology
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US07/913,936 external-priority patent/US4946974A/en
Application filed by Massachusetts Institute Of Technology filed Critical Massachusetts Institute Of Technology
Publication of WO1988000190A1 publication Critical patent/WO1988000190A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/16—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by esterified hydroxyl radicals

Definitions

  • Optically active compounds have increasingly gained importance as the ability to manipulate the synthesis of other optically active compounds has improved.
  • a compound is optically active if its atoms are not superimposable upon those of its mirror image.
  • Isomers that are mirror images of each other are called enantiomers.
  • Enantiomers have the same physical properties except for this difference in geometrical shape, i.e. mirror image. This difference however, has Important consequences.
  • Obtaining asymmetric molecules has traditionally involved physically or chemically resolving the desired molecule from a racemic mixture of the two different optical forms.
  • a second method the chiral pool method, involves using naturally occurring asymmetric molecules as building blocks for the desired asymmetric molecule.
  • a third method has been developed which involves controlling the steps of the reaction so that only the desired enantiomer is produced (See U.S. Patent No. 4,471,130).
  • the titanium-catalyzed asymmetric epoxidation of allylic alcohols has been important in further refining the above-described controlled step process.
  • Homochiral glycidol has been useful in the synthesis of ⁇ -adrenergic blocking agents ( ⁇ -blockers).
  • glycidol is difficult to store and isolate because it is unstable.
  • the in situ derivation of glycidol where the unstable glycidol is derivatized after completion of the asymmetric epoxidation reaction rather than isolated directly from the reaction mixture has many benefits.
  • the derivatives are easier to handle, and they are more advanced synthetic intermediates than the parent glycidol.
  • the ability to obtain high enantiomeric purity for these glycidol derivatives can vary greatly. With many glycidol derivatives it has proven extremely difficult to improve the enantiomeric purity by crystallization.
  • the (2S)-glycidyl m-nitrobenzenesulfonate preferably is purified to at least about 94% e.e., preferably at least about 96% e.e., and even more preferably at least about 98% e.e. Yields up to 98.8% e.e have been obtained in accord with this invention.
  • the purity of the (2S)-glycidyl p-chlorobenzenesulfonate is preferably at least about 94% e.e. and more preferably at least about 95% e.e.
  • This compound is preferably purified to at least about 90% e.e. and even more preferably to at least about 94% e.e.
  • (2R)-glycidyl m-nitrobenzenesulfonate, (2R)-glycidyl ⁇ -chlorobenzenesulfonate and (2R)-glycidyl 4-chloro-3- nitrobenzenesulfonate can be similarly produced by using (+) -DIPT instead of (-)-DIPT.
  • (2R) compounds can be purified to the same enantiomeric purity as (2S) compounds.
  • the crystallized compound is stable and can easily be stored at room temperature until its use is desired.
  • the stability of these compounds means that they can be used commercially as "starting materials" in the synthesis of, for example, ⁇ -blockers.
  • starting materials for example, ⁇ -blockers.
  • a convenient, one-pot procedure can be employed to convert the glycidyl m-nitrobenzenesulfonate into an important intermediate to the ⁇ -blocker, propranolol, which can be converted to propranolol by the addition of i PrNH 2 and H 2 O in the reaction mixture.
  • X is m-nitro, p-chloro or 4-chloro-3- nltrobenzenesulfonate substituent
  • ArOH is an aromatic alcohol. Any aromatic alcohol capable of displacing the sulfonate moiety can be used in the reaction to create the desired intermediate. Preferable aromatic alcohols are those that yield desired ⁇ -blockers upon subsequent reaction with a predetermined amine. The appropriate amine to use can be readily determined by the person of ordinary skill in the art.
  • Crushed 3 ⁇ molecular sieves (Aldrich Chemical Co.) were activated by heating in a vacuum oven at 160oC and 0.05 mm Hg for at least 8 hours.
  • Diisopropyl tartrate and titanium (IV) isopropoxide (Aldrich) were distilled under vacuum and were stored under an inert atmosphere. Allyl alcohol and cumene hydroperoxide (tech., 80%, Aldrich) were dried prior to use over 3 ⁇ molecular sieves, but otherwise used as received.
  • Dichloromethane (EM Reagent) was not distilled, but was also dried over 3 ⁇ molecular sieves.
  • 1-Naphthol (Aldrich) was sublimed prior to use.
  • reaction mixture (stock solution A) (43 ml) was transferred into a 100-ml round-bottomed flask using a syringe, and triethylamine (4.2 ml, 2.05 g, 30 mmol) was added at -20°C, followed by addition of m-nitrobenzenesulfonyl chloride (4.43 g., 20 mmol) as a solution in 8 ml dichloromethane. The flask was stoppered and transferred to a freezer at -20oC.
  • the reaction mixture was diluted with water (5 ml) and extracted with ether (3 x 10 ml). The combined extracts were washed with sat. brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give crude crystalline glycidyl 1-naphthyl ether (98.8% e.e.). The e.e. was determined by NMR analysis (DCI 3 ) of the Mosher ester, which was prepared from the crude glycidyl 1-naphthyl ether according to the method described in Example 1.
  • (2S) -Glycidyl 4-chloro-3-nitrobenzenesulfonate was prepared using 4-chloro-3-nitrobenzenesulfonyl chloride instead of p-toluenesulfonyl chloride, according to the method described in Example 1.
  • Crude crystals mp 49-54°C, 41% yield which were obtained by the crystallization of an oil from diethyl etherpet, ether mixture, were recrystallized from ethanol-ethyl acetate mixture to give pure crystals, mp 54.7-55.2°C, 94% e.e.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Epoxy Compounds (AREA)

Abstract

Les dérivés optiquement actifs de glycidol décrits, soit du m-nitrobenzènesulfonate de (2S) et (2R) glycidyle, du p-chlorobenzènesulfonate de (2S) et (2R) glycidyle et du 4-chloro-3-nitrobenzènesulfonate de (2S) et (2R peuvent être rapidement cristallisés pour atteindre un degré élevé de pureté énantiomorphe. Leur utilisation dans d'autres réactions de synthèse est également décrite.
PCT/US1987/001523 1986-06-25 1987-06-24 Derives optiquement actifs de glycidol WO1988000190A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US87817686A 1986-06-25 1986-06-25
US878,176 1986-06-25
US913,936 1986-10-01
US07/913,936 US4946974A (en) 1986-10-01 1986-10-01 Optically active derivatives of glycidol

Publications (1)

Publication Number Publication Date
WO1988000190A1 true WO1988000190A1 (fr) 1988-01-14

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1987/001523 WO1988000190A1 (fr) 1986-06-25 1987-06-24 Derives optiquement actifs de glycidol

Country Status (2)

Country Link
CA (1) CA1340738C (fr)
WO (1) WO1988000190A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991010642A1 (fr) * 1990-01-22 1991-07-25 Nobel Chemicals Ab Procede de preparation d'amines homochirates et procede de preparation d'intermediaires pour la preparation desdites amines et intermediaires fabriques selon ce procede
EP0441471A1 (fr) * 1990-01-26 1991-08-14 Zeneca Limited Résolution optique
WO1993004054A1 (fr) * 1991-08-22 1993-03-04 Syracuse University Procede et appareil de synthese de stereo-isomeres de derives de glycidol isomeriquement tres purs
US8703948B2 (en) 2006-11-28 2014-04-22 Janssen Pharmaceutica Nv Salts of 3-(3-amino-2-(R)-hydroxy-propyl)-1-(4-fluoro-phenyl)-8-(8-methyl-naphthalen-1-ylmethyl)-1,3,8-triaza-spiro[4.5]decan-4-one
US8741916B2 (en) 2007-04-09 2014-06-03 Janssen Pharmaceutica Nv 1,3,8-trisubstituted-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as ligands of the ORL-1 receptor
US8778956B2 (en) 2002-09-09 2014-07-15 Janssen Pharmaceutica Nv Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2755290A (en) * 1953-10-26 1956-07-17 Shell Dev Esters of sulfonic acids and certain epoxy-substituted alcohols and method for theirpreparation
US3998790A (en) * 1970-02-18 1976-12-21 Aktiebolaget Hassle Phenoxy-hydroxypropylamines, their preparation, and method and pharmaceutical preparations for treating cardiovascular diseases
US4145442A (en) * 1972-04-04 1979-03-20 Aktiebolaget Hassle Phenoxy-hydroxypropylamines, their preparation, and method and pharmaceutical preparations for treating cardiovascular diseases
US4210653A (en) * 1978-06-27 1980-07-01 Merck & Co., Inc. Pyridyloxypropanolamines
EP0071251A1 (fr) * 1981-07-29 1983-02-09 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Aminoglucosides et leur emploi
US4471130A (en) * 1980-08-06 1984-09-11 The Board Of Trustees Of The Leland Stanford Junior University Method for asymmetric epoxidation
EP0157623A2 (fr) * 1984-03-31 1985-10-09 Kowa Company, Ltd. Isomères optiquement actifs de dérivés de benzopyranne utiles pour le traitement de malaises cardiovasculaires

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2755290A (en) * 1953-10-26 1956-07-17 Shell Dev Esters of sulfonic acids and certain epoxy-substituted alcohols and method for theirpreparation
US3998790A (en) * 1970-02-18 1976-12-21 Aktiebolaget Hassle Phenoxy-hydroxypropylamines, their preparation, and method and pharmaceutical preparations for treating cardiovascular diseases
US4145442A (en) * 1972-04-04 1979-03-20 Aktiebolaget Hassle Phenoxy-hydroxypropylamines, their preparation, and method and pharmaceutical preparations for treating cardiovascular diseases
US4210653A (en) * 1978-06-27 1980-07-01 Merck & Co., Inc. Pyridyloxypropanolamines
US4471130A (en) * 1980-08-06 1984-09-11 The Board Of Trustees Of The Leland Stanford Junior University Method for asymmetric epoxidation
EP0071251A1 (fr) * 1981-07-29 1983-02-09 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Aminoglucosides et leur emploi
EP0157623A2 (fr) * 1984-03-31 1985-10-09 Kowa Company, Ltd. Isomères optiquement actifs de dérivés de benzopyranne utiles pour le traitement de malaises cardiovasculaires

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Bulletin of the Chemical Society of Japan, Volume 39, published March 1966, N. NAKABAYASHI et al., "Some Reactions of the Glycidyl Esters of Sulfonic Acids", see pages 413-417. *
CHEMICAL ABSTRACTS, Volume 61, No. 6, issued 14 September 1964 (Columbus, Ohio, USA), ICHIKAWA, "Reactions of Aliphatic Amines with Epoxypropane Derivatives and their Products. I. Reactions of Aliphatic Amines with Epoxypropane Derivatives", see page 7008, column 2, the Abstract No. 7008d. *
Journal of Organic Chemistry, Volume 50, published 1985, ALDRICH, "Chiral Building Blocks", see entire document. *
Journal of the American Chemical Society, Volume 101, published 20 June 1979, D.E. McCLURE et al., "Mode of Nucleophilic Addition to Epichlorohydrin and Related Species: Chiral Aryloxy-methyloxiranes", see pages 3666-3668. *
Memoirs of the Faculty of Science, Volume 14, published 1983, M. MISHIMA et al., "Leaving Group Effects on the Acetolysis of Neophyl Arenesulfonates", see pages 199-210. *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991010642A1 (fr) * 1990-01-22 1991-07-25 Nobel Chemicals Ab Procede de preparation d'amines homochirates et procede de preparation d'intermediaires pour la preparation desdites amines et intermediaires fabriques selon ce procede
EP0441471A1 (fr) * 1990-01-26 1991-08-14 Zeneca Limited Résolution optique
WO1993004054A1 (fr) * 1991-08-22 1993-03-04 Syracuse University Procede et appareil de synthese de stereo-isomeres de derives de glycidol isomeriquement tres purs
US8778956B2 (en) 2002-09-09 2014-07-15 Janssen Pharmaceutica Nv Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
US8703948B2 (en) 2006-11-28 2014-04-22 Janssen Pharmaceutica Nv Salts of 3-(3-amino-2-(R)-hydroxy-propyl)-1-(4-fluoro-phenyl)-8-(8-methyl-naphthalen-1-ylmethyl)-1,3,8-triaza-spiro[4.5]decan-4-one
US8741916B2 (en) 2007-04-09 2014-06-03 Janssen Pharmaceutica Nv 1,3,8-trisubstituted-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as ligands of the ORL-1 receptor

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