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Methyl Acrylate → (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-((E)-2-methoxycarbonyl-vinyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 409464
ノート
印刷プレビュー

反応式

HRID 409464 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=2)[C:14]2[N:19]=[CH:18][C:17](Br)=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH2:36][CH3:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[C:67]([O:71][CH3:72])(=[O:70])[CH:68]=[CH2:69]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=2)[C:14]2[N:19]=[CH:18][C:17](/[CH:69]=[CH:68]/[C:67]([O:71][CH3:72])=[O:70])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH2:36][CH3:37])=[O:7])([CH3:4])([CH3:3])[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 59614321(2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 86648398(2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-((E)-2-methoxycarbonyl-vinyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester
収率 75%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

(2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (300 mg, 0.5 mmol), palladium(II) acetate (15 mg, 0.05 mmol), tri(o-tolyl)phosphine (36 mg, 0.1 mmol), triethylamine (0.2 mL, 1.5 mmol), and methyl acrylate (0.15 mL, 1.5 mmol) are dissolved in DMF (5 mL) and heated in a microwave at 150° C. for 30 minutes. The reaction mixture is filtered through Celite with EtOAc and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-((E)-2methoxycarbonyl-vinyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (225 mg, 75%).

後処理

  1. filtrationThe reaction mixture is filtered through Celite with EtOAc
  2. concentrationconcentrated under reduced pressure
  3. customThe residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc)

出典と根拠

ORDレコード
ord-1fe5cdf4336a4c55b0c4555ecc74b26b
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08759365B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート