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

HRID 553438ノート

反応式

HRID 553438 の反応式
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]

参加物

6

反応物 2

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

生成物 1

HCID 224993072-Thiazolecarboxylic acid, 4-(1-methylethyl)-収率 71.2%

試薬・触媒・溶媒 3

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

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c6cd865738604892aaa4a57fb3c67dc9
出典データセット
uspto-grants-2011_11
特許番号
US08048862B2

反応ノート

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