(2S,4RS)-6,6-dimethyl-5-oxo-4-<(methyloxy)carbonyl>-2-heptanoic acid | 185142-04-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,4RS)-6,6-dimethyl-5-oxo-4-<(methyloxy)carbonyl>-2-heptanoic acid
• 英文别名: (2S,3RS)-6,6-Dimethyl-5-oxo-4-(methyloxycarbonyl)-2-heptanoate；(2S)-4-methoxycarbonyl-6,6-dimethyl-5-oxo-2-[(9-phenylfluoren-9-yl)amino]heptanoic acid
• CAS: 185142-04-5
• 化学式: C₃₀H₃₁NO₅
• 分子量: 485.58
• InChiKey: FDDFOKNRQMNCGL-TUXUZCGSSA-N

物化性质

• 沸点：
  676.2±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4RS)-6,6-dimethyl-5-oxo-4-<(methyloxy)carbonyl>-2-heptanoic acid 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 甲醇 为溶剂， 反应 1.67h， 以69%的产率得到(S)-2--3-(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic acid
  参考文献：
  名称：

  Synthesis of (S)-2-Amino-3-(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic Acid

  摘要：

  An efficient method for synthesizing enantiopure isoxazole amino acids has been developed. (2S)-2-Amino-3-(3-tert-tert-butyl-5-oxo-2H-isoxazol-4-yl) propionic acid (1) was synthesized in three steps from L-gamma-methyl N-(9-(9-phenylfluorenyl))glutamate (2) in 46% overall yield. Acylation of the dianion of 2 with pivaloyl chloride provides beta-keto ester 3 in 75% yield after chromatography. (2S)-2-[N-(9-(9-phenylfluorenyl))amino]-3 -(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic acid (4) was isolated as a white crystalline solid from the reaction of 3 with hydroxylamine under basic conditions followed by exposure to HCl. The crystal structure of 4 confirmed the presence of a 3-tert-butyl-4-isoxazol-5(2H)-one. Title compound 1 was obtained by removal of the PhFl protecting group of 4 using either trifluoroacetic acid in CH2Cl2 or lithium in liquid ammonia. Alkylation of 4 with iodomethane provided a mixture containing (2S,4S)-methyl 2-[N-(9-(9-phenylfluorenyl))amino]-3-(3 -tert-butyl-4-methyl-5-oxo-4H-isoxazol-4-yl)propionate (5) and (2S)-methyl 2-[N-(9-(9-phenylfluorenyl))amino]-3-(2-methyl-3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionate (6). Single crystal X-ray analyses of the structures of 4-6 provide insight into the mechanism of alkylation as well as the configurational stability of N-(9-(9-phenylfluorenyl))amino carbonyl compounds.

  DOI：

  10.1021/jo00115a039
• 作为产物：
  描述：

  三甲基乙酰氯 、 L-N-(9-(9-phenylfluorenyl))glutamic acid γ-methylester 在 正丁基锂 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以75%的产率得到(2S,4RS)-6,6-dimethyl-5-oxo-4-<(methyloxy)carbonyl>-2-heptanoic acid
  参考文献：
  名称：

  Synthesis of (S)-2-Amino-3-(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic Acid

  摘要：

  An efficient method for synthesizing enantiopure isoxazole amino acids has been developed. (2S)-2-Amino-3-(3-tert-tert-butyl-5-oxo-2H-isoxazol-4-yl) propionic acid (1) was synthesized in three steps from L-gamma-methyl N-(9-(9-phenylfluorenyl))glutamate (2) in 46% overall yield. Acylation of the dianion of 2 with pivaloyl chloride provides beta-keto ester 3 in 75% yield after chromatography. (2S)-2-[N-(9-(9-phenylfluorenyl))amino]-3 -(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic acid (4) was isolated as a white crystalline solid from the reaction of 3 with hydroxylamine under basic conditions followed by exposure to HCl. The crystal structure of 4 confirmed the presence of a 3-tert-butyl-4-isoxazol-5(2H)-one. Title compound 1 was obtained by removal of the PhFl protecting group of 4 using either trifluoroacetic acid in CH2Cl2 or lithium in liquid ammonia. Alkylation of 4 with iodomethane provided a mixture containing (2S,4S)-methyl 2-[N-(9-(9-phenylfluorenyl))amino]-3-(3 -tert-butyl-4-methyl-5-oxo-4H-isoxazol-4-yl)propionate (5) and (2S)-methyl 2-[N-(9-(9-phenylfluorenyl))amino]-3-(2-methyl-3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionate (6). Single crystal X-ray analyses of the structures of 4-6 provide insight into the mechanism of alkylation as well as the configurational stability of N-(9-(9-phenylfluorenyl))amino carbonyl compounds.

  DOI：

  10.1021/jo00115a039

文献信息

• Synthesis of (S)-2-Amino-3-(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic Acid
  作者：Mohamed Atfani、William D. Lubell

  DOI：10.1021/jo00115a039

  日期：1995.5

  An efficient method for synthesizing enantiopure isoxazole amino acids has been developed. (2S)-2-Amino-3-(3-tert-tert-butyl-5-oxo-2H-isoxazol-4-yl) propionic acid (1) was synthesized in three steps from L-gamma-methyl N-(9-(9-phenylfluorenyl))glutamate (2) in 46% overall yield. Acylation of the dianion of 2 with pivaloyl chloride provides beta-keto ester 3 in 75% yield after chromatography. (2S)-2-[N-(9-(9-phenylfluorenyl))amino]-3 -(3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionic acid (4) was isolated as a white crystalline solid from the reaction of 3 with hydroxylamine under basic conditions followed by exposure to HCl. The crystal structure of 4 confirmed the presence of a 3-tert-butyl-4-isoxazol-5(2H)-one. Title compound 1 was obtained by removal of the PhFl protecting group of 4 using either trifluoroacetic acid in CH2Cl2 or lithium in liquid ammonia. Alkylation of 4 with iodomethane provided a mixture containing (2S,4S)-methyl 2-[N-(9-(9-phenylfluorenyl))amino]-3-(3 -tert-butyl-4-methyl-5-oxo-4H-isoxazol-4-yl)propionate (5) and (2S)-methyl 2-[N-(9-(9-phenylfluorenyl))amino]-3-(2-methyl-3-tert-butyl-5-oxo-2H-isoxazol-4-yl)propionate (6). Single crystal X-ray analyses of the structures of 4-6 provide insight into the mechanism of alkylation as well as the configurational stability of N-(9-(9-phenylfluorenyl))amino carbonyl compounds.
• 5-<i>tert</i>-Butylproline
  作者：Eric Beausoleil、Benoît L'Archevêque、Laurent Bélec、Mohamed Atfani、William D. Lubell

  DOI：10.1021/jo9618738

  日期：1996.1.1

  Steric effects on the isomer equilibrium of amides N-terminal to proline can be explored with 5-alkylprolines having bulky 5-position substituents. Enantiopure 5-tert-butylprolines were thus synthesized from glutamic acid via an acylation/diastereoselective reductive amination sequence. Double deprotonation of gamma-methyl N-(PhF)glutamate (2) with LiN(SiMe(3))(2) and C-acylation with pivaloyl chloride provided beta-keto ester 3, which upon gamma-ester hydrolysis and decarboxylation gave delta-oxo-alpha-[N-(PhF)amino]heptanoic acid (4). Syntheses of (2S,5R)- and (2R, 5S)-N-(BOC)-5-tert-butylprolines ((2S,5R)-1 and (2R,5S)-1) were accomplished by catalytic hydrogenation of their respective (2S)- and (2R)-methyl delta-ore-alpha-[N-(PhF)amino]heptanoates ((2S)-5a and (2R)-5a) in methanol with di-tert-butyl dicarbonate followed by chromatography and ester hydrolysis with potassium trimethylsilanolate. The 5-tert-butylproline cis-diastereomers were proven to be of >99% enantiomeric purity after their conversion to diastereomeric alpha-methylbenzylamides 10. Good diastereoselectivity in favor of the trans-diastereomer was observed when (2S,5S)-5-tert-butylproline was synthesized from (2S)-delta-oxo-alpha-[N-(PkF)amino]heptanoate ((2S)-4) by solvolysis of the PhF group in trifluoroacetic acid and subsequent reduction of 5-tert-butyl-Delta 5-dehydroproline (11) with tetramethylammonium triacetoxyborohydride; however, imino acid 11 was shown to be configurationally labile and racemized under acidic conditions. 5-tert-Butyl-Delta 5-dehydroproline N'-methylamide 15 was configurationally stable in acid, yet preliminary attempts to reduce 15 favored cis-diastereomer 16. Alternatively, enantiopure trans-diastereomer, (2R,5R)-methyl N-(BOC)-5-tert-butylprolinate (9) was prepared by epimerization of(2S,5R)-9. In summary, this synthetic methodology now provides access to all four enantiopure 5-tert-butylproline isomers from inexpensive L- and D-glutamate as chiral educts.