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

HRID 655189노트

반응식

HRID 655189 반응식
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Br)=[CH:6][CH:5]=1.[OH:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]([C:38](=[O:47])/[CH:39]=[CH:40]/[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:22][C:23]([N:25]2[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]2)=[O:24])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][O:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]([C:38](=[O:47])/[CH:39]=[CH:40]/[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:22][C:23]([N:25]3[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]3)=[O:24])=[CH:17][CH:16]=2)=[CH:6][CH:5]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzeneHCID 59212003[(S)-1-(2-{(4-Hydroxyphenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

생성물 1

HCID 86618488[(S)-1-(2-{[4-(4-Trifluoromethoxybenzyloxy)phenyl]-[(E)-(3-phenylacryloyl)]-amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester수율 75%

시약·촉매·용매 3

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

4-Trifluoromethoxybenzyl bromide (17 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 (52 mg, 75%). 1HNMR (300 MHz) (CDCl3) 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), 5.00 (2H, s), 6.37 (1H, d, J=16 Hz), 6.95 (2H, d), 7.18-7.30 (7H, m), 7.32 (2H, d), 7.45 (2H, d) 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-a012b859489f40ee8f8597a7926dc17a
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071582B2

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