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

HRID 1179474노트

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HRID 1179474 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ab442f1db592492f9d662775dfabcda3
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07279494B2

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