Phosphate → 4,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid

HRID 491701

反応式

HRID 491701 の反応式
O.Cl.[NH2:3][C@@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[C:13]#N.P([O-])([O-])([O-])=O.C([O-])(O)=O.[Na+]>CO>[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[C:13]1[S:6][CH2:5][C@H:4]([C:7]([OH:9])=[O:8])[N:3]=1

参加物

6

反応物 4

HCID 1061PhosphateHCID 516892Sodium BicarbonateHCID 30175202,4-DihydroxybenzonitrileHCID 10176341D-Cysteine hydrochloride monohydrate

生成物 1

HCID 1355326814,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid収率 66%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

D-cysteine hydrochloride monohydrate (6.8 g, 38.7 mmol) was added to a solution of 2,4-dihydroxybenzonitrile (3.5 g, 25.9 mmol) prepared in Example 1, in a mixture of degassed methanol (105 ml) and 0.1 M phosphate buffer, pH 5.95 (70 ml). NaHCO3 (3.25 g, 38.7 mmol) was carefully added and the mixture was stirred at 70° C. under Ar for 54 hours. Volatile components were removed under reduced pressure and the solution was acidified with 1 N HCl to pH 2. The resulting brown precipitate was vacuum filtered and the solid was washed with water (40 ml) and ethanol (20 ml). The crude product was dissolved in saturated NaHCO3 (700 ml) and the aqueous solution washed with ethyl acetate (2×200 ml). The aqueous layer was filtered through a fine frit and acidified with 1 N HCl to pH 2. The precipitated product was vacuum filtered. The aqueous layer was extracted with ethyl acetate (4×400 ml), the combined organic extracts were dried (Na2SO4) and the solvent was removed in vacuo. The remaining solid was combined with the precipitated product and dried under high vacuum at 40° C. for 12 hours to give 4,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid (4.08 g, 66%), mp 266-268° C. (dec) [Ind. J. Chem., Vol. 15B, Kishore et al, pages 255-257 (1977) for (L)-isomer: 261-262° C.]. 1H NMR (300 MHz, DMSO-d6) δ 3.61 (m, 2H), 5.38 (dd, 1H, J=7.2/9.4 Hz), 6.31 (d, 1H, J=2.3 Hz), 6.38 (dd, 1H, J=2.3/8.6 Hz), 7.25 (d, 1H, J=8.6 Hz), 10.25 (br s, 1H), 12.60 (br s, 1H), 13.15 (br s,1H). Anal. calc. for C10H9NO4S: C, 50.20, H, 3.79, N, 5.85. Found: C, 50.13, H, 3.82, N, 5.85.

後処理

  1. customVolatile components were removed under reduced pressure
  2. filtrationfiltered
  3. washthe solid was washed with water (40 ml) and ethanol (20 ml)
  4. dissolutionThe crude product was dissolved in saturated NaHCO3 (700 ml)
  5. washthe aqueous solution washed with ethyl acetate (2×200 ml)
  6. filtrationThe aqueous layer was filtered through a fine frit
  7. filtrationfiltered
  8. extractionThe aqueous layer was extracted with ethyl acetate (4×400 ml)
  9. dry with materialthe combined organic extracts were dried (Na2SO4)
  10. customthe solvent was removed in vacuo
  11. customdried under high vacuum at 40° C. for 12 hours

出典と根拠

ORDレコード
ord-b8c668841a5540779e8e6564d51d7c67
出典データセット
uspto-grants-2009_05
特許番号
US07531563B2

関連ノート

読み込み中…