WO2011000532A3 - Method for the enantioselective addition of organometallic carbon nucleophiles to trifluoromethyl ketones and use of the method in the synthesis of hiv reverse transcriptase inhibitors - Google Patents

Method for the enantioselective addition of organometallic carbon nucleophiles to trifluoromethyl ketones and use of the method in the synthesis of hiv reverse transcriptase inhibitors Download PDF

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Publication number
WO2011000532A3
WO2011000532A3 PCT/EP2010/003907 EP2010003907W WO2011000532A3 WO 2011000532 A3 WO2011000532 A3 WO 2011000532A3 EP 2010003907 W EP2010003907 W EP 2010003907W WO 2011000532 A3 WO2011000532 A3 WO 2011000532A3
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WO
WIPO (PCT)
Prior art keywords
group
lower alkyl
alkyl
alkenyl
groups
Prior art date
Application number
PCT/EP2010/003907
Other languages
German (de)
French (fr)
Other versions
WO2011000532A2 (en
Inventor
Michael Nonnenmacher
Jörg Jung
Andreas Meudt
Original Assignee
Archimica Gmbh
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
Application filed by Archimica Gmbh filed Critical Archimica Gmbh
Priority to EP10728609A priority Critical patent/EP2448917A2/en
Publication of WO2011000532A2 publication Critical patent/WO2011000532A2/en
Publication of WO2011000532A3 publication Critical patent/WO2011000532A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The invention relates to a method for producing compounds of the formula A1, wherein the carbon atom to which both the CF3 group and the hydroxy group are bonded is a stereocenter having either the R or the S configuration and wherein R1 and R2 are a C1-C8 alkyl, C3-C8 cycloalkyl, C2-C8 alkenyl, C4-C8 cycloalkenyl, C2-C8 alkynyl, C6-C14 aryl, or C5-C13 heteroaryl group independently of each other, wherein the alkyl, alkenyl, and alkynyl groups are straight-chained or branched and wherein all stated groups are unsubstituted or are mono- or polysubstituted with the same or different substituents selected from the group: halide, NO2, SO3H, SO3Na, SO3K, CN, OH, NH2, NH-lower alkyl, N-di-lower alkyl, COOH, COO-lower alkyl, lower alkyl, and C3-C6 cycloalkyl, and wherein terminal OH-, NH2-, and NH-lower alkyl groups and acidic H atoms are unprotected or are protected with a protective group, wherein a mixture of a zinc(II) salt, an enantiomerically pure or enantiomerically enriched auxiliary of the formula (I), wherein R3 and R4 are C6-C14 aryl, C5-C13 heteroaryl, C1-C8 alkyl, or C2-C8 alkenyl groups or hydrogen independently of each other and R5 and R6 are C6-C14 aryl, C5-C13 heteroaryl, C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl groups or hydrogen independently of each other or R5 and R6 together represent a C3-C7 alkylene or C3-C7 alkenylene group and at least one of the centers C1, C2, preferably both, is a stereocenter regardless of the configuration of the other center and has either the R or the S configuration and a second auxiliary, which is selected from the group comprising the alcohols, phenols, mercaptans, amines, carboxylic acids, urea derivatives, or the heterocycles containing nitrogen, oxygen, or sulfur, is reacted with an organic or inorganic base and then is reacted with an organometallic compound R1 -M in which R1 has the meaning specified above and in which M is selected from the group: lithium, sodium, potassium, magnesium halide, magnesium cyanide, magnesium-lower alkyl-alcoholates, and then is reacted with a trifluoromethyl ketone (II), wherein R2 has the meaning stated above.
PCT/EP2010/003907 2009-07-03 2010-06-25 Method for the enantioselective addition of organometallic carbon nucleophiles to trifluoromethyl ketones and use of the method in the synthesis of hiv reverse transcriptase inhibitors WO2011000532A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10728609A EP2448917A2 (en) 2009-07-03 2010-06-25 Method for the enantioselective addition of organometallic carbon nucleophiles to trifluoromethyl ketones and use of the method in the synthesis of hiv reverse transcriptase inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102009031861.5 2009-07-03
DE102009031861 2009-07-03

Publications (2)

Publication Number Publication Date
WO2011000532A2 WO2011000532A2 (en) 2011-01-06
WO2011000532A3 true WO2011000532A3 (en) 2011-05-05

Family

ID=43086064

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2010/003907 WO2011000532A2 (en) 2009-07-03 2010-06-25 Method for the enantioselective addition of organometallic carbon nucleophiles to trifluoromethyl ketones and use of the method in the synthesis of hiv reverse transcriptase inhibitors

Country Status (2)

Country Link
EP (1) EP2448917A2 (en)
WO (1) WO2011000532A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105523984A (en) * 2015-09-07 2016-04-27 赤峰艾克制药科技股份有限公司 Preparation method of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101970015B (en) 2008-01-08 2014-05-07 兰休斯医疗成像公司 N-alkoxyamide conjugates as imaging agents
ZA200806473B (en) 2008-01-31 2009-04-29 Aptuit Laurus Pvt Ltd An efficient process to induce enantioselectivity in procarbonyl compounds
WO2012097511A1 (en) * 2011-01-19 2012-07-26 Lonza Ltd Dmp-266 by cyclisation
CN109761829A (en) * 2019-02-19 2019-05-17 盐城迪赛诺制药有限公司 A kind of preparation method of high chiral purity efavirenz intermediate

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5519021A (en) * 1992-08-07 1996-05-21 Merck & Co., Inc. Benzoxazinones as inhibitors of HIV reverse transcriptase
WO1998051676A1 (en) * 1997-05-16 1998-11-19 Merck & Co., Inc. Efficient enantioselective addition reaction using an organozinc reagent
WO2009095931A2 (en) * 2008-01-31 2009-08-06 Aptuit Laurus Pvt Ltd An efficient process to induce enantioselectivity in procarbonyl compounds

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL106507A (en) 1992-08-07 1997-11-20 Merck & Co Inc Pharmaceutical compositions containing benzoxazinones and some novel compounds of this type
US5633405A (en) 1995-05-25 1997-05-27 Merck & Co., Inc. Asymmetric synthesis of (-)-6-chloro-4-cyclopropyl-ethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxanzin-2-one
AU2003248217A1 (en) 2003-04-04 2004-10-25 Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences An amino alcohol ligand and its use in preparation of chiral proparglic tertiary alkohols and tertiary amines via enantioselective additon reaction

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5519021A (en) * 1992-08-07 1996-05-21 Merck & Co., Inc. Benzoxazinones as inhibitors of HIV reverse transcriptase
WO1998051676A1 (en) * 1997-05-16 1998-11-19 Merck & Co., Inc. Efficient enantioselective addition reaction using an organozinc reagent
WO2009095931A2 (en) * 2008-01-31 2009-08-06 Aptuit Laurus Pvt Ltd An efficient process to induce enantioselectivity in procarbonyl compounds

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105523984A (en) * 2015-09-07 2016-04-27 赤峰艾克制药科技股份有限公司 Preparation method of (1R,2S)-1-phenyl-2-(1-pyrrolidyl)-1-propanol

Also Published As

Publication number Publication date
EP2448917A2 (en) 2012-05-09
WO2011000532A2 (en) 2011-01-06

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