Toluene → 2-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester

HRID 639869

반응식

HRID 639869 반응식
C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][C:11]([C:13]1([CH:20]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17]([CH3:18])=[CH:16][C:15](=[O:19])[NH:14]1)=[O:12].Cl[Si](C)(C)C.[Cl:40][CH2:41][CH2:42]OS(C(F)(F)F)(=O)=O.C1(C)C=CC=CC=1>O1CCCC1>[CH3:9][O:10][C:11]([C:13]1([CH:20]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:29])[CH3:30])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17](=[CH2:18])[CH:16]([CH2:42][CH2:41][Cl:40])[C:15](=[O:19])[NH:14]1)=[O:12]

참가 물질

7

반응물 5

HCID 1140TolueneHCID 6397ChlorotrimethylsilaneHCID 1005252-Chloroethyl trifluoromethanesulfonateHCID 2724682Lithium diisopropylamide2회HCID 685762772-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester

생성물 1

HCID 685773462-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester수율 59%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

Lithium diisopropylamide solution (0.67 M solution in tetrahydrofuran, 0.09 ml, 0.06 mmol, 1.0 equiv) was added dropwise via syringe to a stirred solution of 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (23 mg, 0.06 mmol, 1.0 equiv) in tetrahydrofuran (1.5 ml) at −78° C. The reaction mixture was stirred at −78° C. for 30 min. Chlorotrimethylsilane (8 μl, 6.8 mg, 0.06 mmol, 1.0 equiv) was added and the resultant solution was stirred at −78° C. for 2.5 h. Another equiv of lithium diisopropylamide solution (0.67 M solution in tetrahydrofuran, 0.09 ml, 0.06 mmol, 1.0 equiv) was added dropwise at −78° C. The reaction mixture was stirred −78° C. for 30 min. A stock solution of trifluoro-methanesulfonic acid 2-chloro-ethyl ester in toluene (2.45 M, 0.1 ml, 0.24 mmol, 4.0 equiv) was added dropwise via syringe at −78° C. The reaction mixture was stirred at −78° C. for 50 min. A buffer solution (pH=7, 5 ml) was added at −78° C. The organic layer was separated, washed with brine solution (5 ml), dried over sodium sulfate and the solids were filtered. The filtrate was concentrated. The residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) to furnish 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester (16 mg, 59%) along with recovered starting material (5 mg, 22%).

후처리

  1. stirringThe reaction mixture was stirred −78° C. for 30 min
  2. stirringThe reaction mixture was stirred at −78° C. for 50 min
  3. customThe organic layer was separated
  4. washwashed with brine solution (5 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationthe solids were filtered
  7. concentrationThe filtrate was concentrated
  8. customThe residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially

출처 및 근거

ORD 기록
ord-76c624c744ae40d089f6380178feeb52
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691896B2

연결된 노트

불러오는 중…