Thionyl Chloride → (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester

HRID 63724노트

반응식

HRID 63724 반응식
[Cl:1][C:2]1[CH:10]=[C:9]([O:11][Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:8]=[C:7]([Cl:22])[C:3]=1[C:4](O)=[O:5].S(Cl)(Cl)=O.Cl.[CH3:28][O:29][C:30](=[O:51])[C@@H:31]([NH2:50])[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([NH:39][C:40](=[O:49])[C:41]2[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][C:42]=2[Cl:48])=[CH:35][CH:34]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.O>[CH3:28][O:29][C:30](=[O:51])[C@@H:31]([NH:50][C:4](=[O:5])[C:3]1[C:7]([Cl:22])=[CH:8][C:9]([O:11][Si:12]([CH:16]([CH3:18])[CH3:17])([CH:19]([CH3:20])[CH3:21])[CH:13]([CH3:14])[CH3:15])=[CH:10][C:2]=1[Cl:1])[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([NH:39][C:40](=[O:49])[C:41]2[C:42]([Cl:48])=[CH:43][CH:44]=[CH:45][C:46]=2[Cl:47])=[CH:35][CH:34]=1

참가 물질

7

반응물 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 23383932methyl (2S)-2-amino-3-{4-[(2,6-dichlorobenzoyl)amino]phenyl}propionate hydrochlorideHCID 866913092,6-Dichloro-4-triisopropylsilanyloxybenzoic acid

생성물 1

HCID 89717659(S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester수율 95%

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매

실험 절차

To a solution of 2,6-dichloro-4-triisopropylsilanyloxy-benzoic acid (3.63 g, 10 mmol) in toluene (50 mL) was added an excess of thionyl chloride (11.89 g, 7.2 mL, 100 mmol) at room temperature. The resulting colorless solution was heated to reflux for 5 h and then it was cooled to room temperature and the solvent and excess thionyl chloride was removed under vacuum. The resulting residue was azeotrophed one time with toluene. Then, the above 2,6-dichloro-4-triisopropylsilanyloxy-benzoic acid chloride was dissolved in dichloromethane (50 mL) and the solid (S)-2-amino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester hydrochloride salt (4.1 g, 10 mmol) and DIPEA (3.87 g, 5.26 mL, 30 mmol) were added at room temperature. The resulting solution was stirred for 15 h at room temperature and water was added (˜200 mL) to the reaction mixture. Then, the organic compound was extracted into dichloromethane (2×150 mL). The combined organic layer was washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude residue which was purified using an ISCO (120 g) column chromatography to obtain 6.48 g (95%) of (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester as a white solid. ES(+)-HRMS m/e calcd. for C33H38Cl4N2O5Si (M+H)+ 711.1377, obsd. 711.1377.

후처리

  1. temperatureThe resulting colorless solution was heated
  2. temperatureto reflux for 5 h
  3. customthe solvent and excess thionyl chloride was removed under vacuum
  4. dissolutionThen, the above 2,6-dichloro-4-triisopropylsilanyloxy-benzoic acid chloride was dissolved in dichloromethane (50 mL)
  5. extractionThen, the organic compound was extracted into dichloromethane (2×150 mL)
  6. washThe combined organic layer was washed with brine solution
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationFiltration and concentration
  9. customgave the crude residue which
  10. customwas purified

출처 및 근거

ORD 기록
ord-e35ab3d3011c42808cf26512419d1bc2
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447035B2

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