Sulfuric Acid → 3-(4-Chlorobenzyl)-3-formamidocyclobutanecarboxylic acid

HRID 1778596ノート

反応式

HRID 1778596 の反応式
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][C:7]2(O)[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8]2)=[CH:4][CH:3]=1.[C-]#[N:18].[K+].OS(O)(=O)=O.[C:25]([OH:31])(C(F)(F)F)=O>>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][C:7]2([NH:18][CH:25]=[O:31])[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8]2)=[CH:4][CH:3]=1

参加物

5

反応物 4

HCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 9032Potassium CyanideHCID 816983983-(4-Chlorobenzyl)-3-hydroxycyclobutanecarboxylic acid

生成物 1

HCID 895142413-(4-Chlorobenzyl)-3-formamidocyclobutanecarboxylic acid収率 45%

反応条件

温度
0 °C

実験手順

A solution of 3-(4-chlorobenzyl)-3-hydroxycyclobutanecarboxylic acid (1 g, 4.17 mmol) in TFA (17.5 mL) was charged with KCN (813 mg, 12.5 mmol), cooled to 0° C. and treated with H2SO4 (3.5 mL) dropwise. The cooling bath was removed and stirring was continued for 1.5 h. Once the reaction was complete, the mixture was re-cooled to 0° C. diluted with water, and extracted with diethyl ether. The organic layer was washed successively with 1M NaOH and saturated aqueous sodium chloride. The solution was dried over MgSO4, filtered and concentrated. Purification by flash column chromatography (gradient 1-20% methanol in dichloromethane) afforded the subject compound (500 mg, 45% yield). 1H NMR (DMSO-d6, 600 MHz) δ 12.15 (bs, 1H), 8.38 (s, 1H), 7.88 (d, J=1.13 Hz, 1H), 7.36-7.32 (m, 4H), 2.94-2.89 (m, 1H), 2.57-2.53 (m, 1H), 2.36-2.32 (m, 1H), 2.26-2.22 (m, 1H), 2.03-1.96 (m, 1H), 1.95-1.88 (m, 2H). ESI MS found for C13H14ClNO3 m/z [266.1 (M−1)].

後処理

  1. customThe cooling bath was removed
  2. temperaturethe mixture was re-cooled to 0° C.
  3. additiondiluted with water
  4. extractionextracted with diethyl ether
  5. washThe organic layer was washed successively with 1M NaOH and saturated aqueous sodium chloride
  6. dry with materialThe solution was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by flash column chromatography (gradient 1-20% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-18be15a21d7f4e07adde8fbaa26048fc
出典データセット
uspto-grants-2016_02
特許番号
US09266908B2

反応ノート

読み込み中…