(R,R)-6-fluoro-2-(oxiran-2-yl)-chromane-4-one | 797054-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (R,R)-6-fluoro-2-(oxiran-2-yl)-chromane-4-one
• 英文别名: (2R)-6-fluoro-2-[(2R)-oxiran-2-yl]-2,3-dihydrochromen-4-one
• CAS: 797054-30-9
• 化学式: C₁₁H₉FO₃
• 分子量: 208.189
• InChiKey: QDLVHMDXRZTVAD-GHMZBOCLSA-N

物化性质

• 沸点：
  352.1±42.0 °C(Predicted)
• 密度：
  1.426±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R,R)-6-fluoro-2-(oxiran-2-yl)-chromane-4-one 、 (S,R)-2-(2-benzylamino-1-hydroxy-ethyl)-6-fluoro-chroman-4-one 反应 0.25h， 以100%的产率得到N-benzyl-N-[(R,R)-1-hydroxy-2-(6-fluoro-chroman-4-one-2-yl)]-N-[(S,R)-1-hydroxy-2-(6-fluoro-chroman-4-one-2-yl)]-amine
  参考文献：
  名称：

  [EN] NEW PROCESS FOR THE PREPARATION OF RACEMIC ([2S[2R*[R[R*]]]] and ([2R[2S*[S[S*]]]]-(±)- alpha,alpha' -[imino-bis(methylene)]bis[6-fluoro­chroman-2-methanol] AND ITS PURE [2S[2R*[R[R*]&
  [FR] NOUVEAU PROCEDE DE PREPARATION DE ([2S[2R*[R[R*]]]] ET ([2R[2S*[S[S*]]]]-(+/-)- 20040521US4654362AVAN LOMMEN GUY R E [BE], et al198703311528DA1DAJ. HENDRICKX ET AL.: "LOCATION OF THE OH FUNCTIONS IN HYDROXYLATED METABOLITES OF NEBIVOLOL", JOURNAL OF CHROMATOGRAPHY A, vol. 729, no. 1+2, 1996, GB, pages 341 - 354, XP002270638J. HENDRICKX ET AL.LOCATION OF THE OH FUNCTIONS IN HYDROXYLATED METABOLITES OF NEBIVOLOLJOURNAL OF CHROMATOGRAPHY AGB19967291+2341354353VA1,54,55A

  摘要：

  用于制备化合物（I）的混合对映体（[2S[2R*[R[R*]]]]-和([2R[2S*[S[S*]]]]-(±)- α,α' -[亚胺-双(亚甲基)]双[6-氟基-色苷-2-甲醇]的过程及其纯度（[2S[2R*[R[R*]]]]-和([2R[2S*[S[S*]]]]-对映体化合物的特征在于所述产物是从4-氟苯酚或4-氟苯甲醚经过结晶的、具有光学活性的中间体制备而成。

  公开号：

  WO2004041805A1
• 作为产物：
  描述：

  (R,R)-6-fluoro-{2-[(4-methyl-phenyl)-sulphonyl-oxy]-1-hydroxyethyl}-chroman-4-one 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以61%的产率得到(R,R)-6-fluoro-2-(oxiran-2-yl)-chromane-4-one
  参考文献：
  名称：

  [EN] NEW PROCESS FOR THE PREPARATION OF RACEMIC ([2S[2R*[R[R*]]]] and ([2R[2S*[S[S*]]]]-(±)- alpha,alpha' -[imino-bis(methylene)]bis[6-fluoro­chroman-2-methanol] AND ITS PURE [2S[2R*[R[R*]&
  [FR] NOUVEAU PROCEDE DE PREPARATION DE ([2S[2R*[R[R*]]]] ET ([2R[2S*[S[S*]]]]-(+/-)- 20040521US4654362AVAN LOMMEN GUY R E [BE], et al198703311528DA1DAJ. HENDRICKX ET AL.: "LOCATION OF THE OH FUNCTIONS IN HYDROXYLATED METABOLITES OF NEBIVOLOL", JOURNAL OF CHROMATOGRAPHY A, vol. 729, no. 1+2, 1996, GB, pages 341 - 354, XP002270638J. HENDRICKX ET AL.LOCATION OF THE OH FUNCTIONS IN HYDROXYLATED METABOLITES OF NEBIVOLOLJOURNAL OF CHROMATOGRAPHY AGB19967291+2341354353VA1,54,55A

  摘要：

  用于制备化合物（I）的混合对映体（[2S[2R*[R[R*]]]]-和([2R[2S*[S[S*]]]]-(±)- α,α' -[亚胺-双(亚甲基)]双[6-氟基-色苷-2-甲醇]的过程及其纯度（[2S[2R*[R[R*]]]]-和([2R[2S*[S[S*]]]]-对映体化合物的特征在于所述产物是从4-氟苯酚或4-氟苯甲醚经过结晶的、具有光学活性的中间体制备而成。

  公开号：

  WO2004041805A1

文献信息

• Process for preparation of racemic Nebivolol
  申请人：Bader Thomas

  公开号：US20070149612A1

  公开（公告）日：2007-06-28

  A process of making racemic [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α′-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] of the compound of the formula (I) and its pure [2S*[R*[R*[R*]]]]- and [2R*[S*[S*[S*]]]]-enantiomer compounds and pharmaceutically acceptable salts thereof.

  将化合物的立体异构体制备成racemic [2S*[R*[R*[R*]]]]和[2R*[S*[S*[S*]]]]-(±)α,α′-[iminobis(methylene)]bis[6-氟-3,4-二氢-2H-1-苯并吡喃-2-甲醇]的过程，以及其纯[2S*[R*[R*[R*]]]]-和[2R*[S*[S*[S*]]]]-对映体化合物及其药用可接受的盐。
• A process for preparation of racemic nebivolol
  申请人：Cimex Pharma AG

  公开号：EP1803715A1

  公开（公告）日：2007-07-04

  A process of making racemic [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] of the compound of the formula (I) and its pure [2S*[R*[R*[R*]]]]- and [2R*[S*[S*[S*]]]]- enantiomer compounds and pharmaceutically acceptable salts thereof.

  制备式(I)化合物的外消旋[2S*[R*[R*[R*]]]]和[2R*[S*[S*[S*]]]]-(±)α,α'-[亚甲基]双[6-氟-3,4-二氢-2H-1-苯并吡喹啉-2-甲醇]的过程，以及其纯[2S*[R*[R*[R*]]]]和[2R*[S*[S*[S*]]]]对映体化合物及其药学上可接受的盐。
• METHOD FOR PRODUCING NEBIVOLOL
  申请人：Jas Gerhard

  公开号：US20130005001A1

  公开（公告）日：2013-01-03

  The present invention relates to a method for producing racemic nebivolol represented by general formula (I) from the enantiomerically-pure compounds represented by formula (IVa) and (IVb); whereby racemic nebivolol is obtained through mixing enantiomerically-pure d-nebivolol and l-nebivolol which are synthesised independent of each other as enantiomerically-pure compounds through individual coupling of the 4 enantiomerically-pure key intermediates represented by formula (IIa-d) to the corresponding precursors represented by formula (IIIa-d); whereby d-nebivolol (Ia) is obtained through coupling (IIa) to (IIIb) or (IIb) to (IIIa) and l-nebivolol (Ib) is obtained through coupling (IIc) to (IIId) or (IId) to (IIIc), and PG in the intermediates represented by formula (IIa-d) is a hydrogen atom or an amine protection group, and X in the precursors represented by formula (IIIa-d) is a halogen atom, a hydroxyl group, an acyl group, an alkylsulfonyloxy group or an arylsulfonyloxy group, whereby intermediate (IIa) is formed from (IIIa), intermediate (IIb) is formed from (IIIb), intermediate (IIc) is formed from (IIIc), and intermediate (IId) is formed from (IIId), whereby the precursors represented by formula (IIIa) and (IIId) originate from the ketone precursor represented by formula (IVa), and the precursors represented by formula (IIIb) and (IIIc) originate from the ketone precursor represented by formula (IVb), and Z in the ketone precursors (IVa,b) is a halogen atom, a hydroxyl function, an acyl group, an alkylsulfonyloxy group or an arylsulfonyloxy group.

  本发明涉及一种从化学式（IVa）和（IVb）所代表的对映纯化合物中生产化学式（I）所代表的混合型尼倍洛尔的方法；通过将化学式（IIa-d）所代表的4个对映纯中间体与化学式（IIIa-d）所代表的相应前体进行个体的偶联，将对映纯d-尼倍洛尔和l-尼倍洛尔合成为对映纯化合物，从而获得混合型尼倍洛尔。其中，通过将（IIa）与（IIIb）或（IIb）与（IIIa）偶联可得到d-尼倍洛尔（Ia），通过将（IIc）与（IIId）或（IId）与（IIIc）偶联可得到l-尼倍洛尔（Ib）。在化学式（IIa-d）所代表的中间体中，PG为氢原子或胺保护基，在化学式（IIIa-d）所代表的前体中，X为卤原子、羟基、酰基、烷基磺酰氧基或芳基磺酰氧基。其中，中间体（IIa）由（IIIa）形成，中间体（IIb）由（IIIb）形成，中间体（IIc）由（IIIc）形成，中间体（IId）由（IIId）形成。化学式（IIIa）和（IIId）所代表的前体源自化学式（IVa）所代表的酮前体，化学式（IIIb）和（IIIc）所代表的前体源自化学式（IVb）所代表的酮前体。化学式（IVa，b）中的Z为卤原子、羟基、酰基、烷基磺酰氧基或芳基磺酰氧基。
• PROCESS FOR PREPARATION OF RACEMIC NEBIVOLOL
  申请人：Bader Thomas

  公开号：US20090048457A1

  公开（公告）日：2009-02-19

  A process of making racemic [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α′-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] of the compound of the formula (I) and its pure [2S*[R*[R*[R*]]]]- and [2R*[S*[S*[S*]]]]-enantiomer compounds and pharmaceutically acceptable salts thereof.

  制备(±)α,α′-[亚氨基双(亚甲基)]双[6-氟-3,4-二氢-2H-1-苯并吡喃-2-甲醇]的外消旋体[2S*[R*[R*[R*]]]]和[2R*[S*[S*[S*]]]]的过程，以及该化合物的纯[2S*[R*[R*[R*]]]]-和[2R*[S*[S*[S*]]]]-对映体化合物及其药学上可接受的盐。
• US7560575B2
  申请人：——

  公开号：US7560575B2

  公开（公告）日：2009-07-14