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

HRID 655189ノート

反応式

HRID 655189 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a012b859489f40ee8f8597a7926dc17a
出典データセット
uspto-grants-2011_12
特許番号
US08071582B2

反応ノート

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