Hydrochloric Acid → 4-(4-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid

HRID 601849ノート

反応式

HRID 601849 の反応式
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][CH:7]2[C:14]3[CH:13]=[C:12]([C:15]([O:17]C)=[O:16])[N:11](S(C4C=CC(C)=CC=4)(=O)=O)[C:10]=3[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[OH-].[K+].[Li+].[OH-].Cl>C1COCC1.CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[C:14]3[CH:13]=[C:12]([C:15]([OH:17])=[O:16])[NH:11][C:10]=3[CH2:9][CH2:8]2)=[CH:29][CH:30]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 14797Potassium HydroxideHCID 59180148Methyl 4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

生成物 1

HCID 591801514-(4-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

The title compound was synthesized from methyl 4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate in two steps. First, the starting material's methyl ester was hydrolyzed according to General Procedure 7. In this case, 0.070 g (0.274 mmol) of starting ester and potassium hydroxide (10 M, 0.16 mL, 1.6 mmol) were used. The deprotected methyl ester (4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid) (0.035 g, 0.13 mmol) was then dissolved in THF (3 mL) and MeOH (3 mL), and LiOH (0.055 g, 1.3 mmol) in H2O (3 mL) was added and the reaction stirred at 70° C. for 6 h. The reaction was diluted in 25 mL H2O and acidified to pH 2-3 with 1 N HCl, then extracted with 2×50 mL EtOAc. The organic layer was dried over Na2SO4, concentrated and purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-100% EtOAc/heptane to afford the title compound. 16 mg. 19F NMR δ ppm −102.42 (m, J=5.4) LCMS-MS (ESI−) 258.0 (M−H); HPLC (UV=98.52%), (ELSD=100%).

後処理

  1. extractionextracted with 2×50 mL EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by column chromatography (Isco CombiFlash)
  5. washeluting with a gradient of 0-100% EtOAc/heptane

出典と根拠

ORDレコード
ord-909a791f00404e01a28d16a7a788dc26
出典データセット
uspto-grants-2011_03
特許番号
US07902252B2

反応ノート

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