Hydrochloric Acid → methyl (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)acrylate

HRID 1179474ノート

反応式

HRID 1179474 の反応式
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[F:14][C:15]1[CH:16]=[C:17]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:18]=[CH:19][C:20]=1[CH:21]=O.Cl>CN(C=O)C>[CH2:26]([O:25][C:24]([NH:23][C:17]1[CH:18]=[CH:19][C:20](/[CH:21]=[CH:7]/[C:5]([O:4][CH3:3])=[O:6])=[C:15]([F:14])[CH:16]=1)=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 58978059Benzyl (3-fluoro-4-formylphenyl)carbamate

生成物 1

HCID 58978082methyl (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)acrylate収率 64.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

Sodium hydride (0.513 g of a 60% dispersion, 12.8 mmol) was placed in a flask and washed three times with hexane. The resulting solid was suspended in DMF (10 mL) and cooled to 0° C. Trimethyl phosphonoacetate (2.2 mL, 13.5 mmol) was added dropwise to this suspension to give a clear homogeneous solution. After stirring for another 15 minutes at 0° C., a solution of benzyl 3-fluoro-4-formylphenylcarbamate (3.5 g, 12.8 mmol) in DMF (10 mL) was added dropwise. The resulting orange suspension was allowed to warm slowly to room temperature and stirred for 16 hours. The reaction mixture was poured into 0.5 N HCl and extracted with three portions of dichloromethane. Combined organic phases were washed with saturated NaHCO3, H2O, brine, and dried (MgSO4) filtered and concentrated. The resulting orange solid was washed sequentially with hexane and then 30% ethyl acetate-hexane to provide the title compound as a yellow-orange solid (2.7 g). The washings were concentrated and purified by column chromatography (0-30% ethyl acetate-hexane) to provide an additional 0.95 g of the product.

後処理

  1. washwashed three times with hexane
  2. customto give a clear homogeneous solution
  3. temperatureto warm slowly to room temperature
  4. stirringstirred for 16 hours
  5. extractionextracted with three portions of dichloromethane
  6. washCombined organic phases were washed with saturated NaHCO3, H2O, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washThe resulting orange solid was washed sequentially with hexane

出典と根拠

ORDレコード
ord-ab442f1db592492f9d662775dfabcda3
出典データセット
uspto-grants-2007_10
特許番号
US07279494B2

反応ノート

読み込み中…