Lithium hydroxide, monohydrate → 2-Thiazolecarboxylic acid, 4-(1-methylethyl)-

HRID 553438

Reaktionsgleichung

Reaktionsgleichung von HRID 553438
O.[OH-].[Li+].[CH:4]([C:7]1[N:8]=[C:9]([C:12]([O:14]CC)=[O:13])[S:10][CH:11]=1)([CH3:6])[CH3:5]>O1CCCC1.CO.O>[CH:4]([C:7]1[N:8]=[C:9]([C:12]([OH:14])=[O:13])[S:10][CH:11]=1)([CH3:6])[CH3:5]

Komponenten

6

Edukt 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 10821861Ethyl 4-isopropylthiazole-2-carboxylate

Produkt 1

HCID 224993072-Thiazolecarboxylic acid, 4-(1-methylethyl)-Ausbeute 71,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Lithium hydroxide monohydrate (0.947 g, 22.6 mmol., 1.1 eq.) was added to a solution of ethyl 4-isopropyl-thiazole-2 carboxylate (4.08 g, 20.5 mmol., 1.0 eq.) in tetrahydrofuran (45 mL) and methanol (15 mL). The reaction mixture was stirred at ambient temperature for 15 hours. LCMS analysis of the reaction mixture showed a small amount of methyl ester remaining (trans-esterification from ethyl to methyl ester occurred) so lithium hydroxide monohydrate (86 mg, 2.0 mmol., 0.1 eq.) was added and the reaction mixture stirred for a further 3 hours. The reaction mixture was diluted with water (15 mL) and washed with diethyl ether (40 mL). The aqueous phase was cooled to 0° C., and acidified to pH 3 by slow addition of 1M hydrochloric acid. The aqueous layer was extracted with diethyl ether (3×50 mL). The organic extracts were combined, dried over sodium sulphate, filtered and the solvent removed under vacuum to give a mixture of the title product 2.5 g (71%) and 0.6 g of the decarboxylated by product. The mixture was used in the next step without further purification. 1H NMR (250 MHz, CDCl3) δ ppm 7.29 (s, 1 H) 3.15-3.30 (spt, J=6.85 Hz, 1 H), 1.35 (d, J=6.85 Hz, 6 H). LC-MS: 72% (UV), tR 1.21 min, m/z [M+1]+ 171.95.

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction mixture stirred for a further 3 hours
  3. washwashed with diethyl ether (40 mL)
  4. temperatureThe aqueous phase was cooled to 0° C.
  5. additionacidified to pH 3 by slow addition of 1M hydrochloric acid
  6. extractionThe aqueous layer was extracted with diethyl ether (3×50 mL)
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. customto give

Quellen und Nachweise

ORD-Eintrag
ord-c6cd865738604892aaa4a57fb3c67dc9
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08048862B2

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