TW200413399A - Process for producing 2-[bis(2,2,2-trifluoroethyl)phosphonylmethoxy]ethyl halide - Google Patents
Process for producing 2-[bis(2,2,2-trifluoroethyl)phosphonylmethoxy]ethyl halide Download PDFInfo
- Publication number
- TW200413399A TW200413399A TW92132005A TW92132005A TW200413399A TW 200413399 A TW200413399 A TW 200413399A TW 92132005 A TW92132005 A TW 92132005A TW 92132005 A TW92132005 A TW 92132005A TW 200413399 A TW200413399 A TW 200413399A
- Authority
- TW
- Taiwan
- Prior art keywords
- trifluoroethyl
- bis
- ethyl
- producing
- base
- Prior art date
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- -1 ethyl halide Chemical class 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 19
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims abstract description 9
- 150000002148 esters Chemical class 0.000 claims abstract description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 4
- XBUGKDHALPQOTH-UHFFFAOYSA-N bis(2,2,2-trifluoroethyl) hydrogen phosphate Chemical compound FC(F)(F)COP(=O)(O)OCC(F)(F)F XBUGKDHALPQOTH-UHFFFAOYSA-N 0.000 claims description 3
- LUTWEKBTDWRTSE-UHFFFAOYSA-N 1-chloro-2-(chloromethoxy)ethane Chemical compound ClCCOCCl LUTWEKBTDWRTSE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims 2
- 239000012312 sodium hydride Substances 0.000 claims 2
- BUMGVOTUJCOFDZ-UHFFFAOYSA-N 1-chloro-1-(1-chloropropoxy)propane Chemical class CCC(Cl)OC(Cl)CC BUMGVOTUJCOFDZ-UHFFFAOYSA-N 0.000 claims 1
- PWVCQONOYZFZFV-UHFFFAOYSA-N FC(CP(=O)(CC(F)(F)F)COCCCl)(F)F Chemical group FC(CP(=O)(CC(F)(F)F)COCCCl)(F)F PWVCQONOYZFZFV-UHFFFAOYSA-N 0.000 claims 1
- 229910000105 potassium hydride Inorganic materials 0.000 claims 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims 1
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 abstract description 2
- MDFHMUJOSKTPIX-UHFFFAOYSA-N 2-[2-amino-6-(4-methoxyphenyl)sulfanylpurin-9-yl]ethoxymethylphosphonic acid Chemical compound C1=CC(OC)=CC=C1SC1=NC(N)=NC2=C1N=CN2CCOCP(O)(O)=O MDFHMUJOSKTPIX-UHFFFAOYSA-N 0.000 abstract 1
- IESPNWVSLUTLPN-UHFFFAOYSA-N bis(2,2,2-trifluoroethyl) phosphite Chemical compound FC(F)(F)COP([O-])OCC(F)(F)F IESPNWVSLUTLPN-UHFFFAOYSA-N 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical class CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- UJPMYEOUBPIPHQ-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound CC(F)(F)F UJPMYEOUBPIPHQ-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- ZWAMZDRREBOHIO-UHFFFAOYSA-N 1-ethylpyrene Chemical compound C1=C2C(CC)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 ZWAMZDRREBOHIO-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- DRVMZMGCPWFDBI-UHFFFAOYSA-N 2,2,2-trifluoroethyl dihydrogen phosphate Chemical compound OP(O)(=O)OCC(F)(F)F DRVMZMGCPWFDBI-UHFFFAOYSA-N 0.000 description 1
- CYXIKYKBLDZZNW-UHFFFAOYSA-N 2-Chloro-1,1,1-trifluoroethane Chemical compound FC(F)(F)CCl CYXIKYKBLDZZNW-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005485 electric heating Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- ZMQDTYVODWKHNT-UHFFFAOYSA-N tris(2,2,2-trifluoroethyl) phosphate Chemical compound FC(F)(F)COP(=O)(OCC(F)(F)F)OCC(F)(F)F ZMQDTYVODWKHNT-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4075—Esters with hydroxyalkyl compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Description
200413399 (1) 玖、發明說明 【發明所屬之技術領域】 本發明係有關2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基] 乙基鹵之製造方法,詳細的說係有關熟知之抗病毒劑核苷 磷酸酯有用之合成中間體之上述化合物之新穎合成法。 【先前技術】 已知核苷磷酸酯之特定酯衍生物顯示高經口吸收性有 用於作爲抗HBV劑(專利文獻1)。此等酯之中雙(2,2,2_三 氟化乙基)酯亦爲有效物之一。 核苷磷酸酯之雙(2,2,2-三氟化乙基)酯之合成,可考 慮種種方法,其實用方法之一,已有報告2-[雙(2,2,2-三 氟化乙基)膦醯基甲氧基]乙基鹵以核酸鹼反應之方法(專 利文獻1) ’此2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基]乙 基鹵已有由三(2,2,2-三氟化乙基)磷酸酯與2-氯化乙基甲 基氯醚於無溶媒下,以高溫(160。(:)條件反應而得之報告 (專利文獻1)。但,於16(TC加熱時,以常壓工業的溫水 加熱爲不可能’例如必要以高壓水蒸氣或電熱等熱媒加熱 等之裝置’更且反應器亦不得不設計能耐其條件,成爲高 成本之要因。又,此反應,隨著有害物質,亦爲環境污染 物質之1-氯-2,2,2-三氟乙烷之發生,必要將其捕獲,成爲 工業的實施上須極迫對應的事務。 【專利文獻1】 曰本特開平9-255695號公報 -5- (2) (2)200413399 【發明內容】 〔發明之揭示〕 本發明者等,爲解決上述課題經深入硏究結果,發現 可於接近室溫之溫度反應,亦無產生:[-氯_2,2,2_三氟乙 烷,得到收率良好目的物之2-[雙(2,2,2-三氟化乙基)膦醯 基甲氧基]乙基鹵之方法,完成本發明。 即,本發明之要旨係如以下所Μ。 (1) .於鹼的存在下’雙(2,2,2-三氟化乙基)磷酸酯與2-鹵化乙基氯甲基醚反應之2-[雙(2,2,2_三氟化乙基)膦酿基 甲氧基]乙基鹵之製造方法。 (2) ·如上述第1項記載之方法,其中2-[雙(2,2,2 -三氟 化乙基)膦醯基甲氧基]乙基鹵爲2-[雙(2,2,2-三氟化乙基) 膦醯基甲氧基]乙基氯者。 (3) ·含於鹼之存在下,雙(2,2,2-三氟化乙基)磷酸酯與 2 -氯化乙基氯甲基醚反應,製造2-[雙(2,2,2 -三氟化乙基) 膦醯基甲氧基]乙基氯之步驟,製造2 -氨基- 6- (4 -甲氧基苯 硫基)-9-[2-(磷甲氧基)乙基]嘌呤雙(2,2,2-三氟化乙基)酯 之方法。 (4) ·如上述第1至第3項中任一項之方法,其中鹼爲 選自氫氧化鈉及氫氧化鉀者。 (5) ·如上述第1至第3項中任一項之方法,其中鹼爲 氫氧化鈉者。 -6- (3) 200413399 [以寶施發明之最佳型態〕 &下詳細的說明有關本發明。 本發明,於鹼的存在下,雙(2,2,2 -三氟化乙基)磷酸 酉旨與鹵化乙基氯甲基醚反應製造2-[雙(2,2,2-三氟化乙 基)膦醯基甲氧基]乙基鹵之方法,如以下所述。 Ο HP: 二 OCH2CF3 och2cf3 ο X 〜〇“丨 + <ChH;cCfF; X 〜0J、=;CCFF33 (但是,Μ爲鹼,X所示爲氯、溴、碘等之鹵原子) 即,雙(2,2,2-三氟化乙基)磷酸酯於適當的溶劑中, 與鹼反應,成爲該鹽後,以原樣與2-鹵化乙基氯甲基醚 反應,得到2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基]乙基 鹵之方法。 上述之鹼,可列舉如金屬鈉、金屬鉀、氫氧化鈉、氫 氧化鉀、鋰二異丙基胺(LDA)等之金屬類,或三乙基胺等 之三烷基胺,DBN、DBU等之有機鹼等,以氫氧化鈉、氫 氧化鉀爲理想,特別以氫氧化鈉爲理想。 反應無特別限制,可於-50 °C〜lOOt:反應,以-20 °C 〜50°C爲特別理想。 (4) (4)200413399 可使用之溶劑可列舉如乙基酸、丙基醚、四氫咲喃 (THF)1苯、二甲[乙月青、DMF、二頻完、醋酸乙 酯、丙酮、甲乙基酮等。 所得之目的物,通吊之分離精製方法,例如可適當的 選擇以蒸餾、色譜吸附法、萃取等分離精製,粗生成物亦 可原樣提供使用。 上述所得之2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基] 乙基鹵可利用於日本特開平9-2 5 5 695號記載之作爲抗 HBV劑有效化合物2 -氨基- 6- (4 -甲氧基苯硫基磷 甲氧基)乙基]嘌呤雙(2,2,2_三氟化乙基)酯之製造。製造 2-[雙(2,2,2 -三氟化乙基)膦醯基甲氧基]乙基鹵後之製造步 驟可依日本特開平9 - 2 5 5 6 9 5號公報之方法爲準實施。 【實施方式】 以下由實施例更詳細說明本發明,在不超越本發明之 宗旨下,不限定於以下實施例。 實施例1 於氮氣環境下,6.08g(純度換算量)(253mmol)氫氧化 鈉,465ml甲苯於攪拌下,於室溫(24〜26°C)入 59.17g(純 度換算量)(240mmol)雙(2,2,2-三氟化乙基)磷酸酯。滴入 終了後,於36〜40 °C反應30分鐘,將反應液冷卻’於2〜5 °C滴入31.04g(241mmol)2 -氯化乙基氯甲基醚。滴入終了 後,於0〜5 t進行攪拌反應4小時30分鐘。反應終了 -8- (5) (5)200413399 後,反應液恢復至室溫,添加44ml水及3 8ml飽和食鹽 水。於分液漏斗中混合攪拌靜置分離甲苯層及水層後,回 收甲苯層以蒸發器濃縮至60ml。甲苯溶液添加145ml乙 腈及73mln-庚烷,於分液漏斗中攪拌靜置分離乙腈層及 η-庚烷層。回收乙腈層,以蒸發器濃縮,取得72.3 2g純 度90.13%之2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基]乙基 氯(純度換算收率8 0 · 0 %)。 使用如上述所得之2_[雙(2,2,2-三氟化乙基)膦醯基甲 氧基]乙基氯,依日本特開平9-25 5 695號公報之方法可製 造2-氨基-6-(4-甲氧基苯硫基)-9-[2-(磷甲氧基)乙基]嘌呤 雙(2,2,2-三氟化乙基)酯。 〔產業上之利用領域〕 依本發明可提供新穎優效果醫藥品有用之合成中間體 之2-[雙(2,2,2 -二氣化乙基)隣釀基甲氧基]乙基鹵之製造 方法。 本發明以特定之形態詳細說明,在不漂離本發明意圖 之範圍可有種種變更及變形,業者應可明瞭。 又本申請係以2002年1 1月15日申請之日本專利申 請(日本特願2002-3 32163號)爲基礎,援用其全部之引 用。 -9-
Claims (1)
- (1) (1)200413399 拾、申請專利範圍 1. 一種2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基]乙 基鹵之製造方法,其特徵爲於鹼存在下,使雙(2,2,2-三氟 化乙基)磷酸酯與2-鹵化乙基氯甲基醚鈉進行反應者。 2. 如申請專利範圍第1項之2-[雙(2,2,2-三氟化乙 基)膦醯基甲氧基]乙基鹵之製造方法,其中2-[雙(2,2,2-三氟化乙基)膦醯基甲氧基]乙基鹵爲2-[雙(2,2,2-三氟化 乙基)鱗釀基甲氧基]乙基氯者。 3. —種2 -胺基- 6- (4 -甲氧基本硫基)-9-[2-(憐甲氧基) 乙基]嘌呤雙(2,2,2-三氟化乙基)酯之製造方法,其特徵爲 含有於鹼之存在下,使雙(2,2,2-三氟化乙基)磷酸酯與2-氯化乙基氯甲基醚進行反應,製造2-[雙(2,2,2-三氟化乙 基)鱗酿基甲氧基]乙基氣之步驟者。 4. 如申請專利範圍第1至第3項中任一項之方法, 其中鹼爲選自氫化鈉及氫化鉀者。 5 . 如申請專利範圍第1至第3項中任一項之方法, 其中鹼爲氫化鈉者。 -10- 200413399 柒、指定代表圖: (一) 、本案指定代表圖為:無 (二) 、本代表圖之元件代表符號簡單說明:無捌、本案若有化學式時,請揭示最能顯示發明特徵的化學 式: 無-4-
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CN105254671A (zh) * | 2015-11-04 | 2016-01-20 | 天津市亨必达化学合成物有限公司 | 一种制备阿米福韦的方法 |
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WO2003028737A1 (en) * | 2001-08-30 | 2003-04-10 | Mitsubishi Pharma Corporation | Anti-viral agents and in-vitro method for the identification of candidates able to inhibit binding of polymerase to epsilon |
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CN105254671A (zh) * | 2015-11-04 | 2016-01-20 | 天津市亨必达化学合成物有限公司 | 一种制备阿米福韦的方法 |
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