ZA200205878B

ZA200205878B - Asymmetric synthesis of pregabalin.

Asymmetric synthesis of pregabalin. Download PDF

Info

Publication number: ZA200205878B
Authority: ZA; South Africa
Prior art keywords: formula; cation; cyano; pregabalin; alkyl
Prior art date: 2000-01-27

Application number

ZA200205878A

Other languages

English (en)

Inventor

Burk Mark Joseph

Goel Om Prakash

Hoekstra Marvin Simon

Mich Thomas Frederick

Mulhern Thomas Arthur

Ramsden James Andrew

Original Assignee

Warner Lambert Co

Priority date

2000-01-27

Filing date

2002-07-23

Publication date

2003-07-23

2002-07-23 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2003-07-23 Publication of ZA200205878B publication Critical patent/ZA200205878B/en

Links

AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 title claims description 39
229960001233 pregabalin Drugs 0.000 title claims description 33
238000011914 asymmetric synthesis Methods 0.000 title description 4
238000000034 method Methods 0.000 claims description 45
-1 carboxylate salt Chemical class 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
239000003054 catalyst Substances 0.000 claims description 17
238000005984 hydrogenation reaction Methods 0.000 claims description 17
150000001875 compounds Chemical class 0.000 claims description 14
150000001768 cations Chemical class 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
238000006243 chemical reaction Methods 0.000 claims description 8
239000003446 ligand Substances 0.000 claims description 8
150000001336 alkenes Chemical class 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
239000000203 mixture Substances 0.000 claims description 6
239000010948 rhodium Substances 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 5
230000009467 reduction Effects 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 4
150000001340 alkali metals Chemical class 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
229910052703 rhodium Inorganic materials 0.000 claims description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
150000001342 alkaline earth metals Chemical class 0.000 claims description 3
229910052700 potassium Inorganic materials 0.000 claims description 3
239000011591 potassium Substances 0.000 claims description 3
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical group [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 3
238000011065 in-situ storage Methods 0.000 claims description 2
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical group CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
MGWZYUMZVZMKTN-ZETCQYMHSA-N (3s)-3-cyano-5-methylhexanoic acid Chemical class CC(C)C[C@H](C#N)CC(O)=O MGWZYUMZVZMKTN-ZETCQYMHSA-N 0.000 claims 2
150000003141 primary amines Chemical class 0.000 claims 2
230000005588 protonation Effects 0.000 claims 2
125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
125000003277 amino group Chemical group 0.000 claims 1
150000001733 carboxylic acid esters Chemical class 0.000 claims 1
230000003197 catalytic effect Effects 0.000 claims 1
238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 12
238000003786 synthesis reaction Methods 0.000 description 12
238000009876 asymmetric hydrogenation reaction Methods 0.000 description 11
239000000758 substrate Substances 0.000 description 11
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
125000003118 aryl group Chemical group 0.000 description 7
239000000047 product Substances 0.000 description 7
206010010904 Convulsion Diseases 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
239000004912 1,5-cyclooctadiene Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 5
230000008569 process Effects 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
108091022930 Glutamate decarboxylase Proteins 0.000 description 4
238000013459 approach Methods 0.000 description 4
210000004556 brain Anatomy 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000012467 final product Substances 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000002858 neurotransmitter agent Substances 0.000 description 3
230000020477 pH reduction Effects 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000002699 waste material Substances 0.000 description 3
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 2
UWCWUCKPEYNDNV-LBPRGKRZSA-N 2,6-dimethyl-n-[[(2s)-pyrrolidin-2-yl]methyl]aniline Chemical compound CC1=CC=CC(C)=C1NC[C@H]1NCCC1 UWCWUCKPEYNDNV-LBPRGKRZSA-N 0.000 description 2
CYYDDSNDKQYALZ-UHFFFAOYSA-N 2-cyanohexanoic acid Chemical class CCCCC(C#N)C(O)=O CYYDDSNDKQYALZ-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
230000001773 anti-convulsant effect Effects 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
239000002585 base Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
238000010931 ester hydrolysis Methods 0.000 description 2
231100001261 hazardous Toxicity 0.000 description 2
XXROGKLTLUQVRX-UHFFFAOYSA-N hydroxymethylethylene Natural products OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
229960002510 mandelic acid Drugs 0.000 description 2
150000001457 metallic cations Chemical class 0.000 description 2
GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
150000002828 nitro derivatives Chemical class 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
YBRBMKDOPFTVDT-UHFFFAOYSA-O tert-butylammonium Chemical compound CC(C)(C)[NH3+] YBRBMKDOPFTVDT-UHFFFAOYSA-O 0.000 description 2
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
AJNZWRKTWQLAJK-KLHDSHLOSA-N (2r,5r)-1-[2-[(2r,5r)-2,5-dimethylphospholan-1-yl]phenyl]-2,5-dimethylphospholane Chemical compound C[C@@H]1CC[C@@H](C)P1C1=CC=CC=C1P1[C@H](C)CC[C@H]1C AJNZWRKTWQLAJK-KLHDSHLOSA-N 0.000 description 1
PPIBJOQGAJBQDF-VXNVDRBHSA-N (4r,5s)-4-methyl-5-phenyl-1,3-oxazolidin-2-one Chemical compound C[C@H]1NC(=O)O[C@H]1C1=CC=CC=C1 PPIBJOQGAJBQDF-VXNVDRBHSA-N 0.000 description 1
239000001602 (E)-hex-3-enoic acid Substances 0.000 description 1
JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical group C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
MGWZYUMZVZMKTN-UHFFFAOYSA-N 3-cyano-5-methylhexanoic acid Chemical compound CC(C)CC(C#N)CC(O)=O MGWZYUMZVZMKTN-UHFFFAOYSA-N 0.000 description 1
YYMLUQVUARAJKK-UHFFFAOYSA-N 3-hydroxy-4-methyl-2-methylidenepentanenitrile Chemical compound CC(C)C(O)C(=C)C#N YYMLUQVUARAJKK-UHFFFAOYSA-N 0.000 description 1
PKNTXEJOWDTDLN-UHFFFAOYSA-N 4-methyl-2-methylidenepentanenitrile Chemical compound CC(C)CC(=C)C#N PKNTXEJOWDTDLN-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
238000005712 Baylis-Hillman reaction Methods 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
108090000489 Carboxy-Lyases Proteins 0.000 description 1
XXHDAWYDNSXJQM-UHFFFAOYSA-N Chloride-3-Hexenoic acid Natural products CCC=CCC(O)=O XXHDAWYDNSXJQM-UHFFFAOYSA-N 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
238000006105 Hofmann reaction Methods 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
206010061296 Motor dysfunction Diseases 0.000 description 1
229910018830 PO3H Inorganic materials 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
229910006069 SO3H Inorganic materials 0.000 description 1
208000027520 Somatoform disease Diseases 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
239000012190 activator Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000005910 alkyl carbonate group Chemical group 0.000 description 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
230000000573 anti-seizure effect Effects 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
230000003925 brain function Effects 0.000 description 1
244000309464 bull Species 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
230000006315 carbonylation Effects 0.000 description 1
238000005810 carbonylation reaction Methods 0.000 description 1
150000007942 carboxylates Chemical group 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000012777 commercial manufacturing Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
230000002920 convulsive effect Effects 0.000 description 1
YPJHNVOLWRBDQA-UHFFFAOYSA-N cyano hex-2-enoate Chemical compound CCCC=CC(=O)OC#N YPJHNVOLWRBDQA-UHFFFAOYSA-N 0.000 description 1
SGDINNZGYDHHKM-UHFFFAOYSA-N dilithium;trimethylsilylazanide Chemical compound [Li+].[Li+].C[Si](C)(C)[NH-].C[Si](C)(C)[NH-] SGDINNZGYDHHKM-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
NBLCLAYEJWJGJL-UHFFFAOYSA-N ethyl 2-cyano-5-methylhexanoate Chemical compound CCOC(=O)C(C#N)CCC(C)C NBLCLAYEJWJGJL-UHFFFAOYSA-N 0.000 description 1
IFOIXEQWPBMPJK-UHFFFAOYSA-N ethyl 3-cyano-5-methylhex-3-enoate Chemical compound CCOC(=O)CC(C#N)=CC(C)C IFOIXEQWPBMPJK-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
230000001815 facial effect Effects 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical class OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
208000027753 pain disease Diseases 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
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229910000073 phosphorus hydride Inorganic materials 0.000 description 1
239000002243 precursor Substances 0.000 description 1
AYXYPKUFHZROOJ-SSDOTTSWSA-N pregabalin Chemical compound CC(C)C[C@@H](CN)CC(O)=O AYXYPKUFHZROOJ-SSDOTTSWSA-N 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
150000003283 rhodium Chemical class 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
XXHDAWYDNSXJQM-ONEGZZNKSA-N trans-hex-3-enoic acid Chemical compound CC\C=C\CC(O)=O XXHDAWYDNSXJQM-ONEGZZNKSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1