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3,4-Dichlorobenzyl chloride → [(S)-1-(2-{[4-(3,4-Dichlorobenzyloxy)phenyl]-[(E)-(3-phenylacryloyl)]amino}-acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

HRID 468612
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HRID 468612 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5]Cl.[OH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]([C:35](=[O:44])/[CH:36]=[CH:37]/[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:19][C:20]([N:22]2[CH2:26][CH2:25][C@H:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:23]2)=[O:21])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]([C:35](=[O:44])/[CH:36]=[CH:37]/[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:19][C:20]([N:22]2[CH2:26][CH2:25][C@H:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:23]2)=[O:21])=[CH:14][CH:13]=1
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참가 물질

7

반응물 3

HCID 76093,4-Dichlorobenzyl chlorideHCID 10796Cesium carbonateHCID 59212003[(S)-1-(2-{(4-Hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

생성물 1

HCID 59212046[(S)-1-(2-{[4-(3,4-Dichlorobenzyloxy)phenyl]-[(E)-(3-phenylacryloyl)]amino}-acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester수율 68%

시약·촉매·용매 3

HCID 67553
Tetrabutylammonium Iodide
촉매
HCID 6228Dimethylformamide용매
HCID 8857Ethyl Acetate용매

실험 절차

3,4-Dichlorobenzyl chloride (15 μL) was added to a mixture of [(S)-1-(2-{(4-hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester 14 (50 mg, 0.11 mmol), cesium carbonate (52 mg, 0.16 mmol) and TBAI (40 mg, 0.11 mmol) in DMF (3 mL). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate and washed with 10% hydrochloric acid (×2) and brine, dried (Na2SO4) and evaporated to dryness. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/petrol (2:1), to afford the title compound as a colourless foam (46 mg, 68%). 1HNMR (300 MHz) (CDCl3) δ 1.41 (9H, s), 1.7-2.2 (2H, m), 3.35-3.8 (4H, m), 4.15-4.35 (2H, m), 4.5 (1H, m), 4.7-4.9 (1H, m), 5.01 (2H, s), 6.35 (1H, d, J=16 Hz), 6.93 (2H, d), 7.2-7.3 (6H, m), 7.37 (2H, d), 7.44 (1H,d), 7.52 (1H, br s) and 7.64 (1H, d, J=16 Hz).

후처리

  1. washwashed with 10% hydrochloric acid (×2) and brine
  2. dry with materialdried (Na2SO4)
  3. customevaporated to dryness
  4. customThe residue was purified by flash column chromatography on silica gel
  5. washeluting with ethyl acetate/petrol (2:1)

출처 및 근거

ORD 기록
ord-4e61a54bc38349ccb196fa777f53035a
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08624022B2

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