Isobutyric Acid → 2,2-Dimethyl-3-(thiophen-2-yl)propanoic acid

HRID 54232

反応式

HRID 54232 の反応式
[H-].[Na+].[CH:3](NC(C)C)(C)C.[C:10]([OH:15])(=[O:14])[CH:11]([CH3:13])[CH3:12].C([Li])CCC.ClC[S:23][C:24]1[CH:29]=[CH:28][CH:27]=CC=1>O1CCCC1.CCCCCC.C(OCC)C.O>[CH3:12][C:11]([CH3:3])([CH2:13][C:27]1[S:23][CH:24]=[CH:29][CH:28]=1)[C:10]([OH:15])=[O:14]

参加物

10

反応物 5

HCID 6590Isobutyric AcidHCID 7912DiisopropylamineHCID 24758Sodium hydrideHCID 81623Chloromethyl phenyl sulphideHCID 178418339Butyllithium

生成物 1

HCID 104877462,2-Dimethyl-3-(thiophen-2-yl)propanoic acid収率 21.6%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
0 °C

実験手順

To a mixture of 1.23 g (41 mmol) of 80% sodium hydride in 50 mL of dry tetrahydrofuran was added 3.88 g (38.3 mmol) of diisopropylamine and then 3.3 g (37.5 mmol) of isobutyric acid. After heating at reflux for 15 min, and cooling to 0° C., 15 mL (37.5 mmol) of a 2.5M n-butyllithium in hexane solution was added over 10 min. After 15 min, the solution was heated to 35° C. for 30 min, cooled to 0° C. and 5.94 g (37.5 mmol) of chloromethylphenyl sulfide was added. After 30 min at 0° C. and 35° C. for 1 hour, the solution was recooled to 0° C., water added and then diethyl ether. The water layer was separated, acidified and extracted with diethyl ether, dried and concentrated to afford 4.23 g of crude product. Recrystallization from methylene chloride/hexane afforded 1.49 g of 2,2-dimethyl-3-(thiophenyl)propionic acid, m/e 211 (M+H). To a mixture of 1.1 g (5.2 mmol) of 2,2-dimethyl-3-(thiophenyl)propionic acid in 12 mL of acetic acid was added 1.8 mL (17.8 mmol) of 30% aqueous hydrogen peroxide. After 10 minutes at room temperature, all the solids dissolved and the solution was heated to reflux for two hours. After cooling in an ice bath, 23 mL of 10% aqueous sodium sulfite was added and the volatiles removed under vacuum. The residue was acidified with 12N aqueous HCl, extracted with ethyl acetate, dried and concentrated to afford 1.23 g of 2,2-dimethyl-3-(phenylsulfonyl)propionic acid, m/e 260 (M+NH4 +).

後処理

  1. temperatureAfter heating
  2. temperatureat reflux for 15 min
  3. temperaturethe solution was heated to 35° C. for 30 min
  4. temperaturecooled to 0° C.
  5. waitAfter 30 min at 0° C.
  6. wait35° C. for 1 hour
  7. customwas recooled to 0° C.
  8. customThe water layer was separated
  9. extractionextracted with diethyl ether
  10. customdried
  11. concentrationconcentrated
  12. customto afford 4.23 g of crude product
  13. customRecrystallization from methylene chloride/hexane

出典と根拠

ORDレコード
ord-6919ee542c3a4d04b7c3e84c66364453
出典データセット
uspto-grants-1997_04
特許番号
US05622949

関連ノート

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