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

HRID 1773833

Reaktionsgleichung

Reaktionsgleichung von HRID 1773833
[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]

Komponenten

9

Edukt 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

Produkt 1

HCID 710141213-(1-hydroxy-ethyl)-5,6-dihydro-4H-cyclopenta[c]thiophene-1-carboxylic acid methyl esterAusbeute 35,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-52e3d5ba9bc3442181ff79193618d9c9
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09255111B2

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