Hydrochloric Acid → 1-(3-(Chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one

HRID 402973

反応式

HRID 402973 の反応式
[OH:1][C:2]([CH3:12])([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[Al+3].[Cl-:14].[Cl-].[Cl-].[CH2:17]=O.Cl.[OH-].[Na+]>C(Cl)(Cl)Cl.O>[Cl:14][CH2:17][C:7]1[CH:6]=[C:5]([C:3](=[O:4])[C:2]([OH:1])([CH3:12])[CH3:11])[CH:10]=[CH:9][CH:8]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 712Formaldehyde2 回HCID 14798Sodium HydroxideHCID 819842-Hydroxy-2-methyl-1-phenylpropan-1-oneHCID 6451240Aluminum(III) Chloride

生成物 1

HCID 866937891-(3-(Chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one収率 77.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6212Chloroform溶媒

反応条件

温度
0 °C

実験手順

Under nitrogen atmosphere 100 grams of Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one) was placed in 2 L of dry chloroform. After the mixture was cooled to 0° C., 480 grams of anhydrous AlCl3 and 55 grams of paraformaldehyde powder were successively added and the resultant mixture was vigorously stirred at 60° C. overnight for 14 hrs (note that HCl gas released from the reaction was neutralized by 2N NaOH solution). An additional portion of 55 grams of paraformaldehyde was added at this point and the reaction was stirred at this temperature for another 12 hrs. The mixture was cooled to room temperature, and under vigorous stirring poured into 3 L of water. The organic layer thus separated was collected, and the aqueous layer was extracted with 1 L of dichloromethane for three times. The combined chloroform and dichloromethane layer was next dried over anhydrous Na2SO4, filtered, and concentrated. The residue was loaded onto silica gel column and gradient eluted by mixtures of hexane/ethyl acetate (V/V=15/1 to 12/1) to give the intermediate 1-(3-(chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one as a light-yellow oil (77.4% yield), and four other by-products A-D (22.6% combined yield). Characterization data for compound A (11.7% yield): 1H NMR (CDCl3, ppm): 8.01 (s, 2H), 7.63 (s, 1H), 4.63 (s, 4H), 3.78 (s, 1H), 1.62 (s, 6H); 13C NMR (CDCl3, ppm): 203.7, 138.5, 135.0, 132.7, 129.7, 76.7, 45.2, 28.3; Compound B (2.6% yield): 1H NMR (CDCl3, ppm): 7.93 (s, 2H), 7.82 (s, 2H), 7.43 (s, 2H), 4.60 (s, 4H), 4.12 (s, 2H), 3.82 (s, 2H), 1.59 (s, 12H); Compound C (3.1% yield): 1H NMR (CDCl3, ppm): 7.89 (dd, 2H), 7.86 (s, 2H), 7.42-7.40 (m, 4H), 4.10 (s, 2H), 4.05 (s, 2H), 1.60 (s, 12H); 13C NMR (CDCl3, ppm): 204.7, 140.8, 134.2, 133.4, 130.1, 128.7, 127.8, 76.5, 41.5, 28.4; Compound D (4.9% yield): 1H NMR (CDCl3, ppm): 10.06 (s, 1H), 8.54 (s, 1H), 8.31 (d, 1H, J=7.5 Hz), 8.06 (d, 1H, J=7.6 Hz), 7.62 (dd, 1H, J=7.5 Hz, J=7.6 Hz), 3.89 (s, 1H), 1.61 (s, 6H); 13C NMR (CDCl3, ppm): 203.4, 191.9, 136.0, 135.5, 135.3, 132.6, 131.5, 128.9, 77.0, 27.9.

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. stirringunder vigorous stirring
  3. customThe organic layer thus separated
  4. customwas collected
  5. extractionthe aqueous layer was extracted with 1 L of dichloromethane for three times
  6. dry with materialThe combined chloroform and dichloromethane layer was next dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washgradient eluted by mixtures of hexane/ethyl acetate (V/V=15/1 to 12/1)
  10. customto give

出典と根拠

ORDレコード
ord-e6d9c9191cf84e4d87a66aeb2f5dfbf7
出典データセット
uspto-grants-2014_06
特許番号
US08742175B2

関連ノート

読み込み中…