Trifluoroacetic acid → 3-Methyl-3(2,4,6-trimethoxyphenylmethylthio)butyric acid

HRID 1057284

反応式

HRID 1057284 の反応式
[SH:1][C:2]([CH3:8])([CH3:7])[CH2:3][C:4]([OH:6])=[O:5].FC(F)(F)C(O)=O.[CH3:16][O:17][C:18]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[C:19]=1[CH2:20]O>C(Cl)Cl>[CH3:7][C:2]([S:1][CH2:20][C:19]1[C:22]([O:28][CH3:29])=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:18]=1[O:17][CH3:16])([CH3:8])[CH2:3][C:4]([OH:6])=[O:5]

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 6025152,4,6-Trimethoxybenzyl alcoholHCID 98127863-Methyl-3-sulfanylbutanoic acid

生成物 1

HCID 154581393-Methyl-3(2,4,6-trimethoxyphenylmethylthio)butyric acid収率 70%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
5 °C

実験手順

To a solution of 3-mercapto-3-methylbutyric acid (Sweetman et al, J. Med Chem., 14:868 (1971), the disclosure of which is incorporated herein by reference in its entirety) (4.6 g, 34 mmol) in methylene chloride (250 mL) under nitrogen and cooled over ice/salt to 5° C. (internal temperature) was added trifluoroacetic acid (82 g, 0.72 mol). No significant temperature rise was noted during the addition. To this was then added dropwise a solution of 2,4,6-trimethoxybenzyl alcohol (Munson et al., J. Org. Chem., 57, 3013 (1992), the disclosure of which is incorporated herein by reference in its entirety) (6.45 g, 32 mmol) in methylene chloride (150 mL) such that the reaction temperature does not rise above 5° C. After the addition was complete, the mixture was stirred for an additional 5 minutes at 5° C. and the volatiles were evaporated in vacuo (toluene or ethyl acetate can be used to assist in the removal of volatile material). The residue was partitioned between diethyl ether and water and the organic phase dried over anhydrous sodium sulfate, filtered and the volatile material evaporated in vacuo. The residue was treated with activated charcoal and recrystalized from diethyl ether/hexane. The product was isolated as a white solid in 70% yield (7 g) mp 103-105° C. 1H NMR(CDCl3) δ 6.12 (s, 2H), 3.80-3.85 (m, 11H), 2.74 (s, 2H), 1.47 (s, 6H). 13C NMR (CDCl3) δ 173.9, 160.6, 158.6, 105.6, 90.5, 55.7, 55.3, 45.9, 43.6, 28.4, 21.0.

後処理

  1. additionNo significant temperature rise was noted during the addition
  2. customdoes not rise above 5° C
  3. additionAfter the addition
  4. customthe volatiles were evaporated in vacuo (toluene or ethyl acetate
  5. customto assist in the removal of volatile material)
  6. customThe residue was partitioned between diethyl ether and water
  7. dry with materialthe organic phase dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customthe volatile material evaporated in vacuo
  10. additionThe residue was treated with activated charcoal
  11. customrecrystalized from diethyl ether/hexane
  12. customThe product was isolated as a white solid in 70% yield (7 g) mp 103-105° C

出典と根拠

ORDレコード
ord-4cf0576f706c467ba4e2c98bb2bd1f7a
出典データセット
uspto-grants-2003_02
特許番号
US06514934B1

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