IL87246A

IL87246A - Process for the production of unsaturated derivatives of 2-amino-alkanoic acid containing phosphorus, new compounds and pharmaceutical preparations containing them

Process for the production of unsaturated derivatives of 2-amino-alkanoic acid containing phosphorus, new compounds and pharmaceutical preparations containing them

Info

Publication number: IL87246A
Authority: IL; Israel
Prior art keywords: amino; lower alkyl; alkyl; hydroxy; substituted
Prior art date: 1987-08-04

Application number

IL8724688A

Other languages

English (en)

Hebrew (he)

Other versions

IL87246A0 (en

Original Assignee

Ciba Geigy Ag

Priority date

1987-08-04

Filing date

1988-07-28

Publication date

1996-07-23

1988-07-28 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1989-03-31 Publication of IL87246A0 publication Critical patent/IL87246A0/xx

1996-07-23 Publication of IL87246A publication Critical patent/IL87246A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 151
238000000034 method Methods 0.000 title claims description 103
230000008569 process Effects 0.000 title claims description 97
239000002253 acid Substances 0.000 title claims description 33
238000004519 manufacturing process Methods 0.000 title claims description 29
229910052698 phosphorus Inorganic materials 0.000 title description 11
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title description 3
239000011574 phosphorus Substances 0.000 title description 3
125000000217 alkyl group Chemical group 0.000 claims abstract description 239
239000000203 mixture Substances 0.000 claims abstract description 109
-1 amino acid compounds Chemical class 0.000 claims abstract description 103
150000003839 salts Chemical class 0.000 claims abstract description 102
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 101
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 91
239000001257 hydrogen Substances 0.000 claims abstract description 76
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 75
125000003545 alkoxy group Chemical group 0.000 claims abstract description 55
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 49
229910052736 halogen Inorganic materials 0.000 claims abstract description 49
150000002367 halogens Chemical class 0.000 claims abstract description 49
150000002431 hydrogen Chemical class 0.000 claims abstract description 49
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 23
125000003277 amino group Chemical group 0.000 claims abstract description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
230000003287 optical effect Effects 0.000 claims abstract description 11
125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
125000003118 aryl group Chemical group 0.000 claims abstract description 9
OKDOWCKDTWNRCB-PTYLAXBQSA-N [(e,4r)-4-amino-5-ethoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound CCOC(=O)[C@H](N)\C=C(/C)CP(O)(O)=O OKDOWCKDTWNRCB-PTYLAXBQSA-N 0.000 claims abstract 3
229910000077 silane Inorganic materials 0.000 claims abstract 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 160
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 109
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 80
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 72
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
125000003282 alkyl amino group Chemical group 0.000 claims description 38
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
238000006243 chemical reaction Methods 0.000 claims description 26
OKDOWCKDTWNRCB-GQCTYLIASA-N [(e)-4-amino-5-ethoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound CCOC(=O)C(N)\C=C(/C)CP(O)(O)=O OKDOWCKDTWNRCB-GQCTYLIASA-N 0.000 claims description 20
239000007858 starting material Substances 0.000 claims description 20
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 18
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 14
125000001160 methoxycarbonyl group Chemical class [H]C([H])([H])OC(*)=O 0.000 claims description 14
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 claims description 13
OKDOWCKDTWNRCB-SSDOTTSWSA-N [(4r)-4-amino-5-ethoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound CCOC(=O)[C@H](N)C=C(C)CP(O)(O)=O OKDOWCKDTWNRCB-SSDOTTSWSA-N 0.000 claims description 12
125000004423 acyloxy group Chemical group 0.000 claims description 12
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
125000005059 halophenyl group Chemical group 0.000 claims description 10
239000002904 solvent Substances 0.000 claims description 10
BDYHNCZIGYIOGJ-RXMQYKEDSA-N (2r)-2-amino-4-methyl-5-phosphonopent-3-enoic acid Chemical compound OP(=O)(O)CC(C)=C[C@@H](N)C(O)=O BDYHNCZIGYIOGJ-RXMQYKEDSA-N 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
239000000126 substance Substances 0.000 claims description 8
BDYHNCZIGYIOGJ-DUXPYHPUSA-N (e)-2-amino-4-methyl-5-phosphonopent-3-enoic acid Chemical compound OP(=O)(O)CC(/C)=C/C(N)C(O)=O BDYHNCZIGYIOGJ-DUXPYHPUSA-N 0.000 claims description 6
125000002252 acyl group Chemical group 0.000 claims description 6
125000005236 alkanoylamino group Chemical group 0.000 claims description 5
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
239000000463 material Substances 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000004442 acylamino group Chemical group 0.000 claims description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000004494 ethyl ester group Chemical group 0.000 claims description 4
239000012433 hydrogen halide Substances 0.000 claims description 4
229910000039 hydrogen halide Inorganic materials 0.000 claims description 4
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
150000008282 halocarbons Chemical class 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
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 claims description 2
CXPMGWPAIXGDBU-XBXARRHUSA-N [(e)-4-amino-2-methyl-5-(2-methylpropoxy)-5-oxopent-2-enyl]phosphonic acid Chemical compound CC(C)COC(=O)C(N)\C=C(/C)CP(O)(O)=O CXPMGWPAIXGDBU-XBXARRHUSA-N 0.000 claims description 2
CEXLPSTVRBWYFE-SOFGYWHQSA-N [(e)-4-amino-5-butoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound CCCCOC(=O)C(N)\C=C(/C)CP(O)(O)=O CEXLPSTVRBWYFE-SOFGYWHQSA-N 0.000 claims description 2
JKKLPTLBOAXMTI-CSKARUKUSA-N [(e)-4-amino-5-hexoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound CCCCCCOC(=O)C(N)\C=C(/C)CP(O)(O)=O JKKLPTLBOAXMTI-CSKARUKUSA-N 0.000 claims description 2
150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 4
229910000042 hydrogen bromide Inorganic materials 0.000 claims 2
YKISDVQNWMCLRI-NSCUHMNNSA-N (e)-2-amino-2-methyl-5-phosphonopent-3-enoic acid Chemical compound OC(=O)C(N)(C)\C=C\CP(O)(O)=O YKISDVQNWMCLRI-NSCUHMNNSA-N 0.000 claims 1
OSJIIRPRSWOLPK-DUXPYHPUSA-N N\C(\C(=O)O)=C\CCP(=O)(O)O Chemical compound N\C(\C(=O)O)=C\CCP(=O)(O)O OSJIIRPRSWOLPK-DUXPYHPUSA-N 0.000 claims 1
UNDVIPRJDSAXGO-VQHVLOKHSA-N [(e)-4-amino-2-methyl-5-oxo-5-pentoxypent-2-enyl]phosphonic acid Chemical compound CCCCCOC(=O)C(N)\C=C(/C)CP(O)(O)=O UNDVIPRJDSAXGO-VQHVLOKHSA-N 0.000 claims 1
OLUILSXZGHFHAI-HWKANZROSA-N [(e)-4-amino-5-methoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound COC(=O)C(N)\C=C(/C)CP(O)(O)=O OLUILSXZGHFHAI-HWKANZROSA-N 0.000 claims 1
BDYHNCZIGYIOGJ-XWCPEMDWSA-N cgp-37849 Chemical compound OP(=O)(O)CC(/C)=C/[C@@H](N)C(O)=O BDYHNCZIGYIOGJ-XWCPEMDWSA-N 0.000 claims 1
WNBNJKWDUCHCHR-FMIVXFBMSA-N methyl (3e)-4-(diethoxyphosphorylmethyl)-2-formamidohepta-3,6-dienoate Chemical compound CCOP(=O)(OCC)C\C(CC=C)=C\C(NC=O)C(=O)OC WNBNJKWDUCHCHR-FMIVXFBMSA-N 0.000 claims 1
230000000717 retained effect Effects 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
239000000243 solution Substances 0.000 description 123
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
238000001704 evaporation Methods 0.000 description 81
230000008020 evaporation Effects 0.000 description 81
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
229910052757 nitrogen Inorganic materials 0.000 description 33
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
239000000741 silica gel Substances 0.000 description 32
229910002027 silica gel Inorganic materials 0.000 description 32
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
239000012074 organic phase Substances 0.000 description 27
238000004587 chromatography analysis Methods 0.000 description 25
238000001816 cooling Methods 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
229910052938 sodium sulfate Inorganic materials 0.000 description 22
235000011152 sodium sulphate Nutrition 0.000 description 22
239000008346 aqueous phase Substances 0.000 description 17
239000000706 filtrate Substances 0.000 description 17
238000005160 1H NMR spectroscopy Methods 0.000 description 16
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
239000000543 intermediate Substances 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
238000003756 stirring Methods 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
150000002148 esters Chemical class 0.000 description 14
238000004458 analytical method Methods 0.000 description 12
239000011780 sodium chloride Substances 0.000 description 12
239000000725 suspension Substances 0.000 description 12
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
XJYNFPFHNCSKPP-HWKANZROSA-N (e)-4-methyl-2-(methylamino)-5-phosphonopent-3-enoic acid Chemical compound CNC(C(O)=O)\C=C(/C)CP(O)(O)=O XJYNFPFHNCSKPP-HWKANZROSA-N 0.000 description 10
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
125000005907 alkyl ester group Chemical group 0.000 description 10
150000001408 amides Chemical class 0.000 description 10
238000001035 drying Methods 0.000 description 10
239000001117 sulphuric acid Substances 0.000 description 10
235000011149 sulphuric acid Nutrition 0.000 description 10
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
238000010828 elution Methods 0.000 description 9
YYRXFAWZLZDPQY-DHZHZOJOSA-N ethyl (e)-5-[bis(2-chloroethoxy)phosphoryl]-2-formamido-4-methylpent-3-enoate Chemical compound CCOC(=O)C(NC=O)\C=C(/C)CP(=O)(OCCCl)OCCCl YYRXFAWZLZDPQY-DHZHZOJOSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 9
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
SJHCUXCOGGKFAI-UHFFFAOYSA-N tripropan-2-yl phosphite Chemical compound CC(C)OP(OC(C)C)OC(C)C SJHCUXCOGGKFAI-UHFFFAOYSA-N 0.000 description 8
PXEMFROPBWDOOK-ZCFIWIBFSA-N (2r)-2-amino-7-phosphonohept-3-enoic acid Chemical compound OC(=O)[C@H](N)C=CCCCP(O)(O)=O PXEMFROPBWDOOK-ZCFIWIBFSA-N 0.000 description 7
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 7
229910052786 argon Inorganic materials 0.000 description 7
239000002585 base Substances 0.000 description 7
239000000470 constituent Substances 0.000 description 7
YXMZCXDFKCARGB-MRXNPFEDSA-N ethyl (2r)-5-di(propan-2-yloxy)phosphoryl-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pent-3-enoate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(=O)OCC)C=C(C)CP(=O)(OC(C)C)OC(C)C YXMZCXDFKCARGB-MRXNPFEDSA-N 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
238000010992 reflux Methods 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
125000004429 atom Chemical group 0.000 description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
238000009835 boiling Methods 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
239000000284 extract Substances 0.000 description 6
230000010354 integration Effects 0.000 description 6
229910052751 metal Inorganic materials 0.000 description 6
239000002184 metal Substances 0.000 description 6
239000003921 oil Substances 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
PAORVUMOXXAMPL-VIFPVBQESA-N (2r)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl chloride Chemical compound CO[C@@](C(Cl)=O)(C(F)(F)F)C1=CC=CC=C1 PAORVUMOXXAMPL-VIFPVBQESA-N 0.000 description 5
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
229920001429 chelating resin Polymers 0.000 description 5
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
239000008101 lactose Substances 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
STNJBCKSHOAVAJ-UHFFFAOYSA-N Methacrolein Chemical compound CC(=C)C=O STNJBCKSHOAVAJ-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
STLGNXYCVPFIKI-FMIVXFBMSA-N [(e)-4-(benzylamino)-5-ethoxy-2-methyl-5-oxopent-2-enyl]phosphonic acid Chemical compound OP(=O)(O)CC(/C)=C/C(C(=O)OCC)NCC1=CC=CC=C1 STLGNXYCVPFIKI-FMIVXFBMSA-N 0.000 description 4
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