PL217068B1 - (2R,S)-2-hydroxy-2-[((R) R,S)-butoksyetoksyfosfinylo]acetic acid and a process for its preparation - Google Patents
(2R,S)-2-hydroxy-2-[((R) R,S)-butoksyetoksyfosfinylo]acetic acid and a process for its preparationInfo
- Publication number
- PL217068B1 PL217068B1 PL402780A PL40278013A PL217068B1 PL 217068 B1 PL217068 B1 PL 217068B1 PL 402780 A PL402780 A PL 402780A PL 40278013 A PL40278013 A PL 40278013A PL 217068 B1 PL217068 B1 PL 217068B1
- Authority
- PL
- Poland
- Prior art keywords
- hydroxy
- acetic acid
- butoxyethoxyphosphinyl
- preparation
- butoksyetoksyfosfinylo
- Prior art date
Links
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title claims description 33
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 5
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 4
- COXSXIJJRSUURN-UHFFFAOYSA-N butyl ethyl hydrogen phosphite Chemical compound CCCCOP(O)OCC COXSXIJJRSUURN-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000004255 ion exchange chromatography Methods 0.000 claims description 3
- 238000004809 thin layer chromatography Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000026731 phosphorylation Effects 0.000 claims 1
- 238000006366 phosphorylation reaction Methods 0.000 claims 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- IQEKRNXJPCBUAT-UHFFFAOYSA-N 2-[hydroperoxy(hydroxy)phosphoryl]acetic acid Chemical compound OOP(O)(=O)CC(O)=O IQEKRNXJPCBUAT-UHFFFAOYSA-N 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- -1 butyl phosphite ethyl acetate Chemical compound 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003579 shift reagent Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Przedmiotem wynalazku jest kwas (2R,S)-2-hydroksy-2-[((P)R,S)-butoksyetoksyfosfinylo]octowy znajdujący zastosowanie jako chiralny odczynnik przesunięcia chemicznego.The present invention relates to (2R, S) -2-hydroxy-2 - [((P) R, S) -butoxyethoxyphosphinyl] acetic acid for use as a chiral chemical shift reagent.
Przedmiotem wynalazku jest również sposób wytwarzania kwasu (2R,S)-2-hydroksy-2-[((P)R,S)-butoksyetoksyfosfinylo]octowego.The invention also relates to a process for producing (2R, S) -2-hydroxy-2 - [((P) R, S) -butoxyethoxyphosphinyl] acetic acid.
Z pracy magisterskiej K. Marczyka pt. ,,Biotransformacje estru kwasu hydroksyfosfonooctowego ze stereogenicznym atomem fosforu” znana jest metoda otrzymywania kwasu (2R,S)-2-hydroksy-2-[((P)R,S)-etoksyfinylofosfinylo]octowego.From K. Marczyk's thesis entitled "Biotransformation of an ester of hydroxyphosphonoacetic acid with a stereogenic phosphorus atom" is a known method for obtaining (2R, S) -2-hydroxy-2 - [((P) R, S) -ethoxifinylphosphinyl] acetic acid.
Procedura otrzymywania estru etylowego kwasu (2R,S)-2-hydroksy-2-[((P)R,S)-etoksyfinylofosfinylo]octowego, została opisana w zgłoszeniach patentowych US nr 2003 130 234, US nr 2003 114 467, US nr 2003 114 486, US nr 2003 100 572 A1, US nr 2003 105 115, US nr 2003 105 065, US nr 2003 100 573.The procedure for the preparation of ethyl ester of (2R, S) -2-hydroxy-2 - [((P) R, S) -ethoxifinylphosphinyl] acetic acid is described in US Patent Applications 2003 130 234, US 2003 114 467, US No. 2003 114 486, US No. 2003 100 572 A1, US No. 2003 105 115, US No. 2003 105 065, US No. 2003 100 573.
W literaturze jest również znana synteza estru metylowego kwasu (2R,S)-2-metoksy-2-[((P)R,S)-etoksyfinylofosfinylo]octowego opisana przez Grossa i współpracowników w Justus Liebigs Annalen der Chemie, 707 (1967) 35-43.The literature also describes the synthesis of (2R, S) -2-methoxy-2 - [((P) R, S) -ethoxifinylphosphinyl] acetic acid methyl ester described by Gross et al. In Justus Liebigs Annalen der Chemie, 707 (1967) 35-43.
Synteza hydroksyfosfonianów z zastosowaniem trietyloaminy jako katalizatora została opisana przez N. A. Caplana i współpracowników w J. Chem. Soc. Perkin Trans I, (2000) 421-437.The synthesis of hydroxyphosphonates using triethylamine as a catalyst has been described by N. A. Caplan et al. J. Chem. Soc. Perkin Trans I, (2000) 421-437.
Synteza fosforynu butylowo-etylowego została opisana przez G. M. Kosolapoffa w J. Am. Chem. Soc., 73 (1951) 4989.The synthesis of butyl ethyl phosphite has been described by G. M. Kosolapoff in J. Am. Chem. Soc., 73 (1951) 4989.
Badania na hydroksyfosfonianach z dwoma centrami stereogenicznymi prowadzone były w zespole prof. dr hab. inż. Pawła Kafarskiego, a rezultaty przedstawione w publikacjach: Majewska P., Kafarski P., Lejczak B.; Polish J. Chem., 79 (2005) str.: 561-566; Majewska P., Kafarski P., Lejczak B., Bryndal I., Lis T.; Tetrahedron: Asymmetry, 17 (2006) str.: 2697-2701; Majewska P., Kafarski P., Lejczak B.; Tetrahedron: Asymmetry, 17 (2006) str.: 2870-2875; Majewska P., Doskocz M., Lejczak B., Kafarski P.; Tetrahedron: Asymmetry, 20 (2009) str.: 1568-1574; Majewska P., Kafarski P., Lejczak B.; Phosphorus, Sulfur and Silicon and the Related Elements, 185 (2010) str.: 1915-1920.Research on hydroxyphosphonates with two stereogenic centers was carried out in the team of Prof. dr hab. Eng. Paweł Kafarski, and the results were presented in the publications: Majewska P., Kafarski P., Lejczak B .; Polish J. Chem., 79 (2005) pp: 561-566; Majewska P., Kafarski P., Lejczak B., Bryndal I., Lis T .; Tetrahedron: Asymmetry, 17 (2006) pp: 2697-2701; Majewska P., Kafarski P., Lejczak B .; Tetrahedron: Asymmetry, 17 (2006) pp: 2870-2875; Majewska P., Doskocz M., Lejczak B., Kafarski P .; Tetrahedron: Asymmetry, 20 (2009) pp: 1568-1574; Majewska P., Kafarski P., Lejczak B .; Phosphorus, Sulfur and Silicon and the Related Elements, 185 (2010) pp: 1915-1920.
Kwas (2R,S)-2-hydroksy-2-[((P)R,S)-butoksyetoksyfosfinylo]octowy oraz sposób jego wytwarzania nie zostały dotychczas opisane w literaturze.(2R, S) -2-hydroxy-2 - [((P) R, S) -butoxyethoxyphosphinyl] acetic acid and its preparation process have not been described in the literature so far.
Istotą wynalazku jest kwas (2R,S)-2-hydroksy-2-[((P)R,S)-butoksyetoksyfosfinylo]octowy o wzorze I.The essence of the invention is (2R, S) -2-hydroxy-2 - [((P) R, S) -butoxyethoxyphosphinyl] acetic acid of formula I.
Wynalazek dotyczy również sposobu wytwarzania nowego kwasu (2R,S)-2-hydroksy-2-[((P)R,S)-butoksyetoksyfosfinylo]octowego o wzorze I i polega na tym, że kwas glioksalowy poddaje się reakcji fosforylacji racemicznym fosforynem butylowo-etylowym, przy czym reakcję prowadzi się w temperaturze pokojowej w obecności trietyloaminy jako katalizatora przez 2 godziny, a następnie powstały produkt oczyszcza się za pomocą chromatografii jonowymiennej.The invention also relates to a process for the preparation of a novel (2R, S) -2-hydroxy-2 - [((P) R, S) -butoxyethoxyphosphinyl] acetic acid of formula I, wherein glyoxylic acid is phosphorylated with racemic butyl phosphite ethyl acetate, the reaction being carried out at room temperature in the presence of triethylamine as a catalyst for 2 hours, and then the resulting product is purified by ion exchange chromatography.
Korzystnie, reakcję kontroluje się przy użyciu chromatografii cienkowarstwowej.Preferably, the reaction is monitored by thin layer chromatography.
Sposób według wynalazku jest przedstawiony w przykładzie wykonania.The method according to the invention is shown in an embodiment.
P r z y k ł a d IP r z k ł a d I
W okrągłodennej kolbie o pojemności 250 ml umieszcza się 3,32 g (20 mmol) fosforynu butylowo-etylowego, 1,84 (20 mmol) kwasu glioksalowego jednowodnego i 2,79 ml (20 mmol) trietyloaminy. Całość miesza się na mieszadle magnetycznym przez 2 godziny, aż do całkowitego rozpuszczenia się jednowodnego kwasu glioksalowego. Przebieg reakcji monitoruje się za pomocą chromatografii TLC. Po tym czasie produkt z mieszaniny reakcyjnej oczyszcza się za pomocą chromatografii jonowymiennej, w wyniku której otrzymuje się 2,93 g czystego kwasu (2R,S)-2-hydroksy-2-[((P)R,S)-butoksyetoksyfosfinylo]octowego, co stanowi 61% wydajności.In a 250 ml round bottom flask are placed 3.32 g (20 mmol) of butyl ethyl phosphite, 1.84 (20 mmol) glyoxylic acid monohydrate and 2.79 ml (20 mmol) of triethylamine. The mixture is stirred on a magnetic stirrer for 2 hours until the glyoxylic acid monohydrate is completely dissolved. The course of the reaction is monitored by TLC chromatography. After this time, the product of the reaction mixture is purified by ion exchange chromatography to obtain 2.93 g of pure (2R, S) -2-hydroxy-2 - [((P) R, S) -butoxyethoxyphosphinyl] acetic acid which is 61% efficiency.
Produkt otrzymany według przykładu posiada następujące właściwości spektralne:The product obtained according to the example has the following spectral properties:
1H NMR (CDCI3, δ, ppm): 0,94 (t, J = 7,3 Hz, 3H, POCH2CH2CH2CH3), 1,37 (t, J = 7,1 Hz, 3H, POCH2CH3 od jednej pary enancjomerów), 1,38 (t, J = 7,1 Hz, 3H, POCH2CH3 od drugiej pary enancjomerów), 1,64-1,75 (m, 2H, POCH2CH2CH2CH3), 4,18-4,34 (m, 4H, POCH2CH2CH2CH3, POCH2CH3), 4,57 (d, J = 16,1 Hz, 1H, PCH). 1 H NMR (CDCl3, δ, ppm): 0.94 (t, J = 7.3 Hz, 3H, POCH2CH2CH2CH3), 1.37 (t, J = 7.1 Hz, 3H, POCH 2 CH 3 by a pair of enantiomers), 1.38 (t, J = 7.1 Hz, 3H, POCH 2 CH 3 from the second pair of enantiomers), 1.64-1.75 (m, 2H, POCH2CH2CH2CH3), 4.18-4, 34 (m, 4H, POCH2CH2CH2CH3, POCH2CH3), 4.57 (d, J = 16.1 Hz, 1H, PCH).
31P NMR (CDCI3, δ, ppm): 16,80. 31 P NMR (CDCl3, δ, ppm): 16.80.
13C NMR (CDCI3, δ, ppm): 13,74 (POCH2CH2CH2CH3), 16,51 (d, J = 6,2 Hz, POCH2CH3), 18,78 (POCH2CH2CH2CH3), 32,62 (d, J = 4,3 Hz, POCH2CH2CH2CH3), 64,62 (d, J = 1,0 Hz, POCH2CH3 od jednej pary enancjomerów), 65,06 (d, J = 1,2 Hz, POCH2CH3 od drugiej pary enancjomerów), 68,21 (d, J = 7,4 Hz, POCH2CH2CH2CH3 od jednej pary enancjomerów), 68,62 (d, J = 156,9 Hz, PCH od 13 C NMR (CDCl3, δ, ppm): 13.74 (POCH2CH2CH2CH3), 16.51 (d, J = 6.2Hz, POCH2CH3), 18.78 (POCH2CH2CH2CH3), 32.62 (d, J = 4 , 3 Hz, POCH2CH2CH2CH3), 64.62 (d, J = 1.0 Hz, POCH2CH3 from one pair of enantiomers), 65.06 (d, J = 1.2 Hz, POCH 2 CH 3 from the second pair of enantiomers), 68.21 (d, J = 7.4 Hz, POCH 2 CH 2 CH 2 CH 3 from one pair of enantiomers), 68.62 (d, J = 156.9 Hz, PCH from
PL 217 068 B1 jednej pary enancjomerów), 68,65 (d, J = 1,5 Hz, POCH2CH2CH2CH3 od drugiej pary enancjomerów), 68,66 (d, J = 156,9 Hz, PCH od drugiej pary enancjomerów), 170,55 (d, J = 10,3 Hz, COOH).PL 217 068 B1 of one pair of enantiomers), 68.65 (d, J = 1.5 Hz, POCH 2 CH 2 CH 2 CH 3 from the second pair of enantiomers), 68.66 (d, J = 156.9 Hz, PCH from the second pair of enantiomers), 170.55 (d, J = 10.3 Hz, COOH).
Claims (3)
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| PL402780A PL217068B1 (en) | 2013-02-15 | 2013-02-15 | (2R,S)-2-hydroxy-2-[((R) R,S)-butoksyetoksyfosfinylo]acetic acid and a process for its preparation |
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| PL402780A PL217068B1 (en) | 2013-02-15 | 2013-02-15 | (2R,S)-2-hydroxy-2-[((R) R,S)-butoksyetoksyfosfinylo]acetic acid and a process for its preparation |
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| PL217068B1 true PL217068B1 (en) | 2014-06-30 |
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