WO2016054564A1 - 3-o-alkylation sélective de méthyle alpha-l-rhamnopyranoside - Google Patents

3-o-alkylation sélective de méthyle alpha-l-rhamnopyranoside Download PDF

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WO2016054564A1
WO2016054564A1 PCT/US2015/053815 US2015053815W WO2016054564A1 WO 2016054564 A1 WO2016054564 A1 WO 2016054564A1 US 2015053815 W US2015053815 W US 2015053815W WO 2016054564 A1 WO2016054564 A1 WO 2016054564A1
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amount
mole
compound
equivalents
alkyl
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PCT/US2015/053815
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English (en)
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Gary D. Crouse
Carl Deamicis
Beth Lorsbach
Jerod Patzner
Andrew Ward
Erich W. BAUM
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Dow Agrosciences Llc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • C07H15/10—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical containing unsaturated carbon-to-carbon bonds

Definitions

  • the invention described herein pertains to processes for selectively alkylating methyl alpha- L-rhamnopyranoside and preparing methyl 3-O-(alkyl or alkenyl) alpha- L- rhamnopyranoside substantially free of 2-O-(alkyl or alkenyl) alpha-L-rhamnopyranoside.
  • Described herein are processes for preparing compounds I or II substantially free of the compounds III or IV, respectively.
  • Advantages of this process relative to prior reported processes include (a) the reaction yields the 3-O-alkylated product with improved yield while maintaining selectivity and (b) the avoidance of stoichiometric amounts of tin. Isolated yields are as high as 90% with >3: 1 selectivity for alkylation at the 3-OH relative to the 2-OH.
  • Described herein is the use of from about 0.5 equivalents to about 3 equivalents of a metal carbonate, from about 0.1 equivalents to about 1 equivalent of a boron promoter, from about 0.1 equivalents to about 2 equivalent of an additive, from about 1 equivalent to about 2 equivalents of an alkylating agent, a polar aprotic solvent, at a temperature of from about 40 °C to about 110 °C at times ranging from about 20 hours to about 72 hours. Under these conditions, high yield and selectivity for 3-O-alkylation over 2-O-alkylation has been observed.
  • Illustrative metal carbonates useful in the processes described here include sodium carbonate, potassium carbonate, cesium carbonate, and the like. It has been discovered that the alkylation reaction does not proceed to an appreciable degree when the metal carbonate is replaced with a tertiary amine base (See Comparative Example CE2, Entry 1). It has also been discovered that a metal carbonate is necessary for the reaction to proceed efficiently (See Comparative Example CE2, Entry 2).
  • Boron promoters used in the processes described herein include optionally substituted phenyl boronic acids and diphenylborinates.
  • Illustrative examples include, phenylboronic acid, 2,6-difluoro-phenylboronic acid, 2-methoxyphenylboronic acid,
  • Additives used in the processes described herein include iodide salts, tertiary amine bases, and transition metal salts.
  • Illustrative examples of additives used in the processes described herein include potassium iodide, tetrabutylammonium iodide, triethylamine, diisopropylamine, copper(II) chloride, copper(II) bromide, copper(II) iodide, copper(I) iodide, copper(I) bromide, copper(I) chloride, copper(I) oxide, zinc(II) acetate, and silver(I) chloride.
  • additives is useful for increasing the rate of the reaction when using activated alkylating agents such as allyl bromide (See Example 6, Entry 3 and 6). It has also been discovered that additives are less effective when non-activated alkylating agents such as iodopropane are employed (See Comparative Example CE2, Entry 6 and Example 6, Entry 1 and Entry 2).
  • Alkylating agents used in the processes described herein include alkyl bromides, alkyl iodides, alkenyl bromides, alkenyl iodides, alkylaryl bromides and alkylaryl iodides.
  • Illustrative examples include bromopropane, iodopropane, allyl bromide, allyl iodide, benzyl bromide, and benzyl iodide.
  • Polar aprotic solvents used in the processes described herein include alkyl nitriles.
  • Illustrative examples include acetonitrile and propionitrile. It has been discovered that use of nitrile solvents provides improved yields compared to the yields obtained with the use of dimethylformamide (See Comparative Example CE2, Entry 5).
  • Described herein is a process for removing the 2-O-(alkyl or alkenyl) isomer formed in the alkylation of methyl alpha-L- rhamnopyranoside. It has been discovered that a simple process comprising an oxidation step can be used to remove the unwanted isomer. Described herein is the process of contacting a solution or suspension of the reaction product formed in the alkylation step with an oxidant that selectively reacts with vicinal hydroxyl groups allowing for the purification of the 3-O-alkylated isomer via aqueous extraction.
  • Described herein is the treatment of a solution or suspension containing a mixture of methyl 3-0-(alkyl or alkenyl) alpha-L-rhamnopyranoside and methyl 2-0-(alkyl or alkenyl) alpha-L-rhamnopyranoside with a solution of suspension of sodium periodate followed by an aqueous extraction to yield the 3-O-alkylated rhamnose derivative substantially free of the 2-O-alkylated isomer. It is appreciated that other oxidants may be used for the selective removal of the undesired isomer. It has been observed that not all oxidizers are suitable (See Comparative Example CE3).
  • Described herein is the treatment of a solution or suspension of methyl 3-0- alkylated rhamnopyranoside, contaminated with from about 5% to about 25% of the 2-0- alkylated rhamnopyranoside, with an aqueous solution or suspension of sodium periodate (from about 1 to about 3 equivalents relative to the amount of 2-0-(alkyl or alkenyl) isomer present).
  • an aqueous solution or suspension of sodium periodate from about 1 to about 3 equivalents relative to the amount of 2-0-(alkyl or alkenyl) isomer present.
  • Illustrative organic solvents for extraction include ethyl acetate, methyl tert-butyl ether, and the like. Described herein is treatment of a dimethylsulfoxide solution of methyl 3-0-(alkyl or alkenyl) rhamnopyranoside which is substantially free of methyl 2-0-(alkyl or alkenyl) rhamnopyranoside with a base such as powdered potassium hydroxide and an additional alkylating agent.
  • additional alkylating agents include methylating agents dimethyl sulfate, iodomethane, bromomethane, chloromethane, methyl trifluoromethylsulfonate, and the like.
  • dimethylsulfoxide solution upon completion of alkylation, with a hydrocarbon or ethereal solvent results in isolation of methyl 3-0-(alkyl or alkenyl) 2,4-di-O-methyl alpha-L- rhamnopyranoside substantially free of methyl 2-0-(alkyl or alkenyl) 2,4-di-O-methyl alpha-L- rhamnopyranoside.
  • Illustrative hydrocarbon solvents include heptane, hexane, cyclohexane, and the like.
  • Illustrative ethereal solvents include diethyl ether, methyl tert-butyl ether, and the like.
  • R is alkyl, alkenyl, or alkylaryl each of which is optionally substituted; the process comprising:
  • R x -X an alkylating agent
  • the amount the alkylating agent is about 1 mole-equivalent to about 2 mole-equivalents based on the amount of compound (A), wherein R 1 is as previously defined and X is CI, Br, or I;
  • an amount of a metal carbonate wherein the amount of the metal carbonate is about 0.5 mole-equivalent to about 3 mole-equivalents based on the amount of compound (A);
  • an amount of a boron promoter wherein the amount of the boron promoter is about 0.1 mole-equivalents to about 1 mole-equivalent based on the amount of compound (A);
  • an amount of an additive wherein the amount of the additive is about 0.2 mole- equivalents to about 2 mole-equivalent based on the amount of compound (A) when Ri-X is activated; or
  • R is alkyl, alkenyl, or alkylaryl each of which is optionally substituted; the process comprising:
  • R is alkyl, alkenyl, or alkylaryl each of which is optionally substituted; and R is alkyl;
  • an amount of an additional alkylating agent R 2 -X 2 , wherein the amount of an additional alkylating agent is about 2 mole-equivalents to about 3 mole-equivalents based on the amount of compound (I),
  • R 2 is as previously defined and X 2 is CI, Br, I, OS(0) 2 CF3, or
  • an amount of a base where the amount of the base is about 3 mole-equivalents to about 4 mole-equivalents based on the amount of compound (I).
  • step (a) • The process of any one of the preceding clauses wherein the polar aprotic solvent of step (a) is acetonitrile or propionitrile.
  • step (a) • The process of any one of the preceding clauses wherein the temperature of step (a) is about 60 °C to about 80 °C.
  • R 1 is a (Ci-C 4 ) alkyl.
  • R 1 -X is a (C 3 ) alkyl iodide.
  • R 1 is a (C 2 -C 4 ) alkenyl.
  • R a is H, F, CH 3 , OCH , or CF , and n is 1 or 2.
  • step (a) is an iodide salt.
  • step (a) is potassium iodide.
  • step (a) is a tertiary amine base.
  • step (a) is triethylamine or diisopropylethylamine.
  • step (a) is a transition metal salt.
  • step (a) is selected from copper(II) chloride, copper(II) bromide, copper(II) iodide, copper(I) iodide, copper(I) bromide, copper(I) chloride, copper(I) oxide, zinc(II) acetate, and silver(I) chloride.
  • step (a) is selected from copper(II) chloride or copper(I) bromide.
  • step (a) • The process of any one of the preceding clauses wherein the temperature of step (a) is from about 20 °C to about 35 °C.
  • step (a) • The process of any one of the preceding clauses wherein the oxidant of step (a) is a periodate salt or manganese dioxide.
  • step (b) • The process of any one of the preceding clauses wherein the polar aprotic solvent of step (b) is dimethylsulfoxide.
  • step (b) • The process of any one of the preceding clauses wherein the temperature of step (b) is from about 20 °C to about 40 °C.
  • step (b) is an inorganic base.
  • step (b) is potassium hydroxide or sodium hydroxide.
  • alkyl includes a chain of carbon atoms, which is optionally branched.
  • alkenyl includes a chain of carbon atoms, which is optionally branched, and includes at least one double bond. It is to be further understood that in certain embodiments, alkyl is advantageously of limited length, (C Cg), (C - C 6 ), and (Q-C. . It is to be further understood that in certain embodiments alkenyl may be advantageously of limited length, including (C 2 -C 6 ), and (C 2 -C4).
  • Illustrative alkyl and alkenyl groups are, but not limited to, methyl, ethyl, n-propyl, isopropyl, w-butyl, isobutyl, sec-butyl, ie/t-butyl, pentyl, 2-pentyl, 3-pentyl, neopentyl, hexyl, heptyl, octyl, and the like, and the corresponding groups containing one or more double bonds, or a combination thereof.
  • aryl includes monocyclic and polycyclic aromatic carbocyclic groups, each of which may be optionally substituted.
  • Illustrative aromatic carbocyclic groups described herein include, but are not limited to, phenyl, naphthyl, and the like.
  • the term "optionally substituted” includes the replacement of hydrogen atoms with other functional groups on radical that is optionally substituted.
  • Such other functional groups illustratively include, but are not limited to, amino, hydroxy, halo, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, heteroarylheteroalkyl, nitro, sulfonyl, sulfonic acids and derivatives thereof, carboxylic acids and derivatives thereof, and the like.
  • any of amino, hydroxy, thio, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl, and/or heteroarylheteroalkyl is optionally substituted.
  • the term "substantially free of when used to describe a compound that may contain some amount of another compound as an impurity or contaminant generally means that the amount of the impurity or contaminant that is present is less than about 3%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less than about 0.25%, or less than about 0.1%.
  • methyl alpha-L-rhamnopyranoside 5.0 g, 28 mmol, 1 equivalent
  • dry dimethylformamide 25 mL
  • 4-fluorophenylboronic acid 0.98 g, 7.0 mmol, 0.25 equivalents
  • potassium carbonate 7.8 g, 56 mmol, 2 equivalents
  • allyl bromide 6.8 g, 56 mmol, 2 equivalents
  • Methyl alpha-L-rhamnopyranoside (5.00 g, 28.1 mmol, 1 equivalent) and phenylboronic acid (3.42 g, 28.1 mmol, 1 equivalent) were dissolved in dry acetonitrile (250 mL) in a round-bottomed flask (500 mL).
  • Cesium carbonate (10.1 g, 30.9 mmol, 1.1 equivalents)
  • potassium iodide (4.66 g, 28.1 mmol, 1 equivalents)
  • allyl bromide (3.16 mL, 36.5 mmol, 1.3 equivalents) were added.
  • the reaction was stirred and heated at 70 °C under nitrogen. After 24 hours, the solution was cooled to room temperature and poured onto water.
  • Methyl alpha-L-rhamnopyranoside (5.00 g, 28.1 mmol, 1 equivalent) and phenylboronic acid (3.42 g, 28.1 mmol, 1 equivalent) were dissolved in dry acetonitrile (250 mL) in a round-bottomed flask (500 mL).
  • Potassium carbonate (4.27 g, 30.9 mmol, 1.1 equivalents)
  • potassium iodide (4.66 g, 28.1 mmol, 1 equivalent)
  • allyl bromide (3.16 mL, 36.5 mmol, 1.3 equivalents) were added.
  • the reaction was stirred and heated at 70 °C under nitrogen for 24 hours. The solution was then cooled and poured onto water.
  • isomer ratio is measured by comparing proton peak areas for the anomeric-OMe substituent.
  • HB diisopropylethylamine
  • KI potassium iodide
  • reaction was monitored by thin layer chromatography (R/for the 2' isomer is 0.25; R/for the 3' isomer is 0.3 using a solvent system consisting of 3:3:3: 1 hexanes:ethyl acetate:dichloromethane:acetone, visualized by phosphomolybdic acid stain.) and by GCMS, which showed no detectable 2-isomer after 24 hours.
  • the black suspension was heated at 75 °C and analyzed by 1H NMR every 3 hours. After the addition of 6.4 equivalents of manganese dioxide and heating for a total of 12 hours, the ratio of 3-0:2-0- allyl isomer was 50: 1 by 1H NMR.
  • the black suspension was cooled to 25 °C and the mixture was vacuum filtered through a plug of Celite® and the Celite® pad rinsed with acetonitrile (2 x 100 mL). The filtrate and rinses were combined (yellow solution) and concentrated to give a light brown oil (19.3 g). Analysis of the brown oil by 1H NMR showed a 50: 1 ratio of 3-0:2-0- allyl isomer with acetonitrile solvent (20% by mass).
  • EXAMPLE 11 Synthesis of methyl 3-O-allyl-2,4-di-0-methyl alpha-L-rhamnopyranoside.
  • EXAMPLE CE1 Synthesis of 3-O-allyl/alkyl-alpha-L-rhamnopyranoside using Onomura conditions.
  • Ratio of isomers was measured by comparing the integral for the anomeric -OMe peaks, which occur at 3.37 and 3.36 ppm, respectively.
  • EXAMPLE CE3 Attempted purification of methyl 3-O-allyl alpha-L-rhamnopyranoside using oxidants other than sodium periodate and manganese dioxide

Abstract

La présente invention concerne des procédés de fabrication de composés utiles pour la production de composés pesticides.
PCT/US2015/053815 2014-10-03 2015-10-02 3-o-alkylation sélective de méthyle alpha-l-rhamnopyranoside WO2016054564A1 (fr)

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US62/059,197 2014-10-03

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009102736A1 (fr) * 2008-02-12 2009-08-20 Dow Agrosciences Llc Compositions pesticides

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009102736A1 (fr) * 2008-02-12 2009-08-20 Dow Agrosciences Llc Compositions pesticides

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHAN LINA ET AL.: "Regioselective alkylation of carbohydrate derivatives catalyzed by diarylborinic acid derivative", ORGANIC LETTERS, vol. 13, no. 12, 2011, pages 3090 - 3093 *
DIMITRIJEVIC ELENA ET AL.: "9-Hetero-10-boraanthracene-derived borinic acid catalysts for regioselective activation of polyols»", CHEMICAL SCIENCE, vol. 4, 2013, pages 3298 - 3303 *
LEE DORIS ET AL.: "Regioselective, Borinic Acid-Catalyzed Monoacylation, Sulfonylation and Alkylation of Diols and Carbohydrates: Expansion of Substrate Scope and Mechanistic Studies", J. AM. CHEM. SOC., vol. 134, no. 19, 2012, pages 8260 - 8267 *

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