Dimethyl Sulfoxide → 5-(4-fluorophenyl)-1-(2-((2S,4S)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide

HRID 893498

反応式

HRID 893498 の反応式
NCC[C@H:4]1[O:9][C:8]2([CH2:14]CCCC2)[O:7][C@@H:6]([CH2:15][C:16]([OH:18])=O)[CH2:5]1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26](=O)[CH:27]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:28]([C:38](=O)C(C)C)[C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:30])=[CH:22][CH:21]=1.C(O[CH2:53][CH3:54])C.[Cl-].[NH4+:56].[CH3:57]S(C)=O>O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:56]([CH2:4][CH2:5][C@H:6]3[CH2:15][C@H:16]([OH:18])[CH2:14][C:8](=[O:9])[O:7]3)[C:38]([CH:53]([CH3:54])[CH3:57])=[C:28]([C:29]([NH:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[O:30])[C:27]=2[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[CH:22][CH:21]=1

参加物

7

反応物 5

HCID 679Dimethyl SulfoxideHCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 99098724-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamideHCID 15045142(2R-cis)-4-(2-aminoethyl)-1,5-dioxaspiro[5.5]undecane-2-acetic acid

生成物 1

HCID 139236655-(4-fluorophenyl)-1-(2-((2S,4S)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
105 °C

実験手順

A solution of 0.31 g (1.21 mmol) of (±)-cis-4-(2-aminoethyl)-1,5-dioxaspiro[5.5]undecane-2-acetic acid and 0.504 g (1.20 mmol) of (±)-4-fluoro-α-[2-methyl-1-oxopropyl]-γ-oxo-N,β-diphenylbenzenebutane-amide mixture of [R-(R*,R*)], [R-(R*,S*)], [S-(R*,R*)] and [S-(R*,S*)] isomers in 5 mL of dimethyl sulfoxide is heated at 105° C. for 15 hours. The solution is cooled and poured into 100 mL of diethyl ether and 50 mL of saturated ammonium chloride in water. The layers are separated and the organic layer washed with water (2×50 mL) and 5% sodium hydroxide solution (2×100 mL--to extract the intermediate acid from unreacted diketone). The aqueous layer is acidified with dilute hydrochloric acid solution, stirred for three hours and extracted with 30 mL of ethyl acetate to remove the protecting group before lactonization. The extract is concentrated and dissolved in 30 mL of ethyl acetate. A drop of concentrated hydrochloric acid is added to the ethyl acetate solution and allowed to stand 18 hours. The solution is concentrated in vacuo and the concentrate is redissolved in 30 mL of ethyl acetate and treated with one drop of concentrated hydrochloric acid. The solution is stirred two hours, concentrated in vacuo, and dissolved in 6 mL of toluene. Trans-(±)-5-(4- fluoro-phenyl)-2-(1-methylethyl)-N,α-diphenyl-1-[2- (tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide crystallizes and is isolated by filtration. A total of 0.155 g of trans-(±)-5-(4- fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide is isolated in two crops.

後処理

  1. temperatureThe solution is cooled
  2. customThe layers are separated
  3. washthe organic layer washed with water (2×50 mL) and 5% sodium hydroxide solution (2×100 mL
  4. extractionto extract the intermediate acid from unreacted diketone)
  5. extractionextracted with 30 mL of ethyl acetate
  6. customto remove the protecting group before lactonization
  7. concentrationThe extract is concentrated
  8. dissolutiondissolved in 30 mL of ethyl acetate
  9. additionA drop of concentrated hydrochloric acid is added to the ethyl acetate solution
  10. waitto stand 18 hours
  11. concentrationThe solution is concentrated in vacuo
  12. dissolutionthe concentrate is redissolved in 30 mL of ethyl acetate
  13. additiontreated with one drop of concentrated hydrochloric acid
  14. stirringThe solution is stirred two hours
  15. concentrationconcentrated in vacuo
  16. dissolutiondissolved in 6 mL of toluene
  17. customTrans-(±)-5-(4- fluoro-phenyl)-2-(1-methylethyl)-N,α-diphenyl-1-[2- (tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide crystallizes
  18. customis isolated by filtration

出典と根拠

ORDレコード
ord-6e6950c24a384245bcccdd5951ebee7f
出典データセット
uspto-grants-1992_06
特許番号
US05124482

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