(S)-3-amino-4,4,4-trifluorobutanoic acid | 151871-99-7

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-3-amino-4,4,4-trifluorobutanoic acid
• 英文别名: (3S)-3-amino-4,4,4-trifluorobutanoic acid
• CAS: 151871-99-7
• 化学式: C₄H₆F₃NO₂
• mdl: MFCD00041413
• 分子量: 157.092
• InChiKey: XRXQOEWWPPJVII-REOHCLBHSA-N

物化性质

• 沸点：
  238.3±40.0 °C(Predicted)
• 密度：
  1.432±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  氯甲酸苄酯 、 (S)-3-amino-4,4,4-trifluorobutanoic acid 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 12.0h， 以56%的产率得到(S)-3-(((Benzyloxy)carbonyl)amino)-4,4,4-trifluorobutanoic acid
  参考文献：
  名称：

  Stereo-regulated synthesis of peptides containing a β-trifluoromethyl-β-amino acid

  摘要：

  For the chemical conversions of a beta-trifluoromethyl-beta-amino acid ((S)-4,4,4-trifluoro-3-aminobutyric acid, 1), such as the N-terminus protection with benzyloxycarbonyl or tert-butoxycarbonyl group, the C-terminus protection with benzyl or tert-butyl group, and peptide elongation at the both termini, highly practical protocols were established. Through these conversions, the stereochemistry of 1 and/or its condensation counterpart was maintained. Because the protocols developed here are indispensable for the application of 1 in peptide engineering, they would expand the utility of 1 and its derivatives. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.08.051
• 作为产物：
  描述：

  methyl (S)-4,4,4-trifluoro-3-aminobutyrate hydrochloride 在 盐酸 、 水 、 methyloxirane 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以84%的产率得到(S)-3-amino-4,4,4-trifluorobutanoic acid
  参考文献：
  名称：

  A practical method to access enantiopure β-perfluoroalkyl-β-amino acids: diastereoselective reduction of cyclic enamino-esters

  摘要：

  A highly practical method to access enantiopure beta-perfluoroalkyl-beta-amino acids was developed, which Could be conducted Without any expensive reagent, special apparatus/technique, nor tedious chromatographic separation. The condensation of methyl 4,4,4-trifluoro-3-oxobutanoate with (S)-2-amino-2-phenylethanol, followed by an intramoleculer transesterification, gave an enamino-ester with a seven-membered ring structure. The hydride reduction of the cyclic enamino-ester proceeded with excellent diastereoselectivity (dr = 95:5-97:3) to give the corresponding cyclic amino-ester. The major isomer of the cyclic amino-ester was readily separated from the minor one and successfully converted into (S)-3-amino-4,4,4-trifluorobutanoic acid (five steps, 38% overall yield, >99% ee). Concerning the key step of this synthesis, the same strategy was applicable to another substrate: the asymmetric hydride reduction of a cyclic enamino-ester with a pentafluoroethyl group also proceeded in excellent diastereoselectivity (dr = 96:4). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.01.159

文献信息

• Asymmetric Mannich reaction between (S)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine and malonic acid derivatives. Stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids
  作者：Norio Shibata、Takayuki Nishimine、Naoyuki Shibata、Etsuko Tokunaga、Kosuke Kawada、Takumi Kagawa、José Luis Aceña、Alexander E. Sorochinsky、Vadim A. Soloshonok

  DOI：10.1039/c3ob42425a

  日期：——

  diastereoselective Mannich additions of malonic acid derivatives to (SS)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine. In the presence of catalytic amounts of inorganic bases, n-BuLi or DMAP, the reaction gives the corresponding (R,SS)-β-aminomalonates in good yield and with diastereoselectivity up to 9/1 dr. In contrast, phosphazene bases favour the formation of the (S,SS)-diastereomer with selectivities

  无机以及有机碱催化被发现是有效的丙二酸衍生物的非对映选择性曼尼希增补（小号小号） - ñ - （叔-butanesulfinyl）-3,3,3- trifluoroacetaldimine。在催化量的无机碱，n- BuLi或DMAP的存在下，反应以高收率和高达9/1 dr的非对映选择性产生相应的（R，S S）-β-氨基丙二酸酯。相反，磷腈碱有利于（S，S S）-非对映异构体，选择性高达99/1。简单地为曼尼希加成反应选择合适的碱催化剂，使我们能够在相应的β-氨基丙二酸酯水解和脱羧后获得对映体纯的（R）-或（S）-构型的3-氨基-4,4,4-三氟丁酸。 。
• Organic base-catalyzed stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids
  作者：Norio Shibata、Takayuki Nishimine、Naoyuki Shibata、Etsuko Tokunaga、Kosuke Kawada、Takumi Kagawa、Alexander E. Sorochinsky、Vadim A. Soloshonok

  DOI：10.1039/c2cc30627a

  日期：——

  base-catalyzed reaction of (S)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine with dialkyl malonates was found to be effective for synthesis of both (S,S(S)) and (R,S(S)) beta-aminomalonates in high yield with good to excellent diastereoselectivity (76-98% de). The products of this Mannich reaction provide direct access to beta-trifluoromethyl-beta-alanine of either (R) or (S) absolute configuration

  发现（S）-N-叔丁烷亚磺酰基（3,3,3）-三氟乙醛亚胺与丙二酸二烷基酯的有机碱催化反应可有效合成（S，S（S））和（R，S（ S））高产的β-氨基丙二酸酯，具有良好至优异的非对映选择性（76-98％de）。该曼尼希反应的产物提供了直接获得（R）或（S）绝对构型的β-三氟甲基-β-丙氨酸的途径。
• Operationally convenient asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid
  作者：Vadim A. Soloshonok、Hironari Ohkura、Manabu Yasumoto

  DOI：10.1016/j.jfluchem.2006.04.004

  日期：2006.7

  An asymmetric synthesis of (S)- and (R)-3-amino-4,4,4-trifluorobutanoic acid via DBU-catalyzed asymmetric 1,3-proton shift transfer reaction of (Z)-3-[(R)-1-phenylethylamino]-4,4,4-trifluoro-N-[(R)-1-phenylethyl]but-2-enamide has been developed. The intermediate Schiff base (S,R′)-9 was found to be relatively configurationally stable under the highly basic reaction conditions allowing preparation of

  的不对称合成（小号） -和（- [R）-3-氨基-4,4,4- trifluorobutanoic通过（DBU催化不对称1,3-质子移转移反应酸Ž）-3 - [（[R ）-已经开发了1-苯基乙基氨基] -4，4，4-三氟-N -[（R）-1-苯基乙基]丁-2-烯酰胺。发现中间体席夫碱（S，R '）- 9在高碱性反应条件下相对构型稳定，从而允许以高化学产率和对映选择性制备目标氨基酸。已证明该方法对于大规模（> 25 g）大规模合成目标β-氨基酸是可行的。
• Kukhar', V. K.; Soloshonok, V. A.; Shvyadas, V. K., Russian Journal of Bioorganic Chemistry, 1993, vol. 19, # 4, p. 233 - 235
  作者：Kukhar', V. K.、Soloshonok, V. A.、Shvyadas, V. K.、Kotik, N. V.、Galaev, I. Yu、et al.

  DOI：——

  日期：——
• Biocatalytic resolution of β-fluoroalkyl-β-amino acids
  作者：Vadim A. Soloshonok、Alexander G. Kirilenko、Nataly A. Fokina、Irine P. Shishkina、Sergey V. Galushko、Valery P. Kukhar、Vytas K. Švedas、Elena V. Kozlova

  DOI：10.1016/0957-4166(94)80063-4

  日期：1994.6

  N-Phenylacetyl derivatives of beta-fluoroalkyl-beta-alanines 6 were synthesized and biocatalytically resolved to the corresponding enantiopure beta-amino acids 7, 9 with the aid of penicillin acylase (EC 3.5.1.11) from Escherichia coli. In substrates 6 the enantioselectivity of the biocatalytic process was practically uninfluenced by the nature of the fluoroalkyl chain. Thus, beta-fluoroalkyl-beta-alanines 7, 9 bearing short (R = CF3, CHF2) or long [C3F7, H(CF2)(4)] chains were prepared in high enantiomeric purity. The (R)-enantiomer was the fast-reacting enantiomer in all cases.