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p-Toluenesulfonic acid → (rac)-(R*,S*)-2-((2-(3,5-difluorophenyl)-2-hydroxy-1-methylethyl)amino)-(R)-2-methylethyl 4-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoate

HRID 2357730
ノート
印刷プレビュー

反応式

HRID 2357730 の反応式
[OH:1][CH2:2][C@H:3]([NH:5][C@@H:6]([CH3:17])[C@@H:7]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=1)[OH:8])[CH3:4].[NH2:18][S:19]([C:22]1[C:23]([Cl:44])=[CH:24][C:25]([NH:37][CH2:38][C:39]2[O:40][CH:41]=[CH:42][CH:43]=2)=[C:26]([CH:36]=1)[C:27]([O:29][CH2:30][CH2:31][CH2:32][C:33](O)=[O:34])=[O:28])(=[O:21])=[O:20].C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C1C=CC=CC=1.C1(C)C=CC=CC=1>[NH2:18][S:19]([C:22]1[C:23]([Cl:44])=[CH:24][C:25]([NH:37][CH2:38][C:39]2[O:40][CH:41]=[CH:42][CH:43]=2)=[C:26]([CH:36]=1)[C:27]([O:29][CH2:30][CH2:31][CH2:32][C:33]([O:1][CH2:2][C@H:3]([NH:5][C@H:6]([CH3:17])[C@H:7]([C:9]1[CH:10]=[C:11]([F:16])[CH:12]=[C:13]([F:15])[CH:14]=1)[OH:8])[CH3:4])=[O:34])=[O:28])(=[O:20])=[O:21]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 6101p-Toluenesulfonic acidHCID 593891294-(5-(Aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoic acidHCID 68457326(rac)-(R*,S*)-2-((2-hydroxy-(R)-1-methylethyl)amino)-1-(3,5-difluorophenyl)propanol

生成物 1

HCID 131728259(rac)-(R*,S*)-2-((2-(3,5-difluorophenyl)-2-hydroxy-1-methylethyl)amino)-(R)-2-methylethyl 4-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoate

試薬・触媒・溶媒

3
HCID 241Benzene溶媒3 回HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

The free base of (rac)-(R*,S*)-2-((2-hydroxy-(R)-1-methylethyl)amino)-1-(3,5-difluorophenyl)propanol (21) (0.023 mole) and benzene (30 mL) (or toluene) is added to a round-bottomed flask. 4-(5-(Aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoic acid (0.025 mole), benzene (30 mL), and p-toluenesulfonic acid (0.026) catalyst is added to the flask. A Dean-Stark trap is filled with benzene, and the contents of the flask is refluxed with stirring for several hours or until no additional water is collected in the trap. The reaction is cooled, extracted with sodium bicarbonate solution, washed with water, and then with a saturated sodium chloride solution. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo to give crude product, which may be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent. The fractions that contain pure product may be combined and spin evaporated in vacuo to give a solid that may be recrystallized to give (rac)-(R*,S*)-2-((2-(3,5-difluorophenyl)-2-hydroxy-1-methylethyl)amino)-(R)-2-methylethyl 4-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)butanoate. See eg., Sandler et al., Organic Functional Group Preparations, p. 249 (1968).

後処理

  1. temperaturethe contents of the flask is refluxed
  2. customis collected in the trap
  3. temperatureThe reaction is cooled
  4. extractionextracted with sodium bicarbonate solution
  5. washwashed with water
  6. dry with materialThe organic layer is dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give crude product, which
  10. custommay be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent
  11. customspin evaporated in vacuo
  12. customto give a solid
  13. customthat may be recrystallized

出典と根拠

ORDレコード
ord-e4290ed1d63945a797ddb9b83c0c0f41
出典データセット
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07763612B2

反応ノート

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