Potassium Carbonate → 3-(1-hydroxy-ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester

HRID 240898

反応式

HRID 240898 の反応式
[H-].[Na+].[CH3:3][O:4][C:5](=[O:8])[CH2:6][SH:7].C([O:12][CH:13]([CH3:22])[C:14](Cl)=[C:15]1[CH2:19][CH2:18][CH2:17][C:16]1=O)(=O)C.C(OC(C)C(C1CCCC=1Cl)=O)(=O)C.C([O-])([O-])=O.[K+].[K+]>O1CCCC1.O.CO>[CH3:3][O:4][C:5]([C:6]1[S:7][C:14]([CH:13]([OH:12])[CH3:22])=[C:15]2[CH2:19][CH2:18][CH2:17][C:16]=12)=[O:8]

参加物

9

反応物 5

HCID 11430Potassium CarbonateHCID 16907Methyl ThioglycolateHCID 24758Sodium hydrideHCID 710141301-(2-Chlorocyclopent-1-enyl)-1-oxopropan-2-yl acetateHCID 710141401-Chloro-1-(2-oxocyclopentylidene)propan-2-yl acetate

生成物 1

HCID 710141213-(1-hydroxy-ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester収率 35.6%

試薬・触媒・溶媒 3

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

実験手順

Add sodium hydride (60% in mineral oil, 2.12 g, 0.053 mol) to a solution of mercapto-acetic acid methyl ester (2.8 g, 0.026 mol) in tetrahydrofuran (100 mL) at −10° C.˜0° C. and stirred the mixture at −10° C.˜0° C. for 1 hour. Then add a mixture of 1-chloro-1-(2-oxocyclopentylidene)propan-2-yl acetate and 1-(2-chlorocyclopent-1-enyl)-1-oxopropan-2-yl acetate (5.47 g, 0.025 mol, 6:1) in tetrahydrofuran (15 mL) at 0° C. After stirring at 0° C. for overnight, dilute the reaction mixture with water and extract with ethyl acetate. The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue and K2CO3 (6.9 g, 0.05 mol) in MeOH (20 mL) is heated at 50° C. overnight. The solvent is removed. The residue is purified by silica gel chromatograph (eluting with 2.5% to 10% ethyl acetate in petroleum ether) to give 3-(1-hydroxy-ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl ester (3.2 g, 14.1 mmol, 35.6% for 2 steps) as yellow oil. 1H NMR (CDCl3, 400 MHz): δ 5.03 (m, 1H), 3.83 (m, 3H), 2.88 (m, 2H), 2.66 (m, 2H), 2.38 (m, 2H), 2.12 (s, 1H), 1.54 (d, J=7.2, 3H).

後処理

  1. additionThen add
  2. stirringAfter stirring at 0° C. for overnight
  3. extractionextract with ethyl acetate
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe solvent is removed
  8. customThe residue is purified by silica gel chromatograph (eluting with 2.5% to 10% ethyl acetate in petroleum ether)

出典と根拠

ORDレコード
ord-b2b184b1b8f449349f0a54e81a862e4d
出典データセット
uspto-grants-2014_02
特許番号
US08648081B2

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