1,4-Dioxane → 2-(4-{[tert-Butoxycarbonyl-(3-tert-butoxycarbonylamino-propyl)-amino]-methyl}-phenyl)-3-methoxy-acrylic acid methyl ester

HRID 717737ノート

反応式

HRID 717737 の反応式
[C:1]([O:5][C:6](=[O:35])[N:7]([CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:8][C:9]1[CH:14]=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:36][O:37][C:38](=[O:44])[C:39](I)=[CH:40][O:41][CH3:42].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:36][O:37][C:38](=[O:44])[C:39]([C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:35])[CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:10][CH:11]=1)=[CH:40][O:41][CH3:42]

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 54067316Methyl 2-iodo-3-methoxyprop-2-enoateHCID 66578953(3-Tert-butoxycarbonylamino-propyl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-carbamic acid tert-butyl ester

生成物 1

HCID 665788052-(4-{[tert-Butoxycarbonyl-(3-tert-butoxycarbonylamino-propyl)-amino]-methyl}-phenyl)-3-methoxy-acrylic acid methyl ester収率 91.3%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

A mixture of (3-tert-butoxycarbonylamino-propyl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-carbamic acid tert-butyl ester (6.00 g, 12.25 mmol), 2-iodo-3-methoxy-acrylic acid methyl ester (4.45 g, 18.38 mmol), K3PO4 (7.79 g, 36.75 mmol), Pd(PPh3)4 (0) (0.68 g, 0.61 mmol), dioxane (60 mL) and water (12 mL) was degassed and heated at 80° C. for 20 h under argon atmosphere. The reaction mixture was diluted with EtOAc (500 mL), washed with water (300 mL) and brine (300 mL). The organic solution was concentrated and purified by flash chromatography (0%-30% EtOAc in heptane) to give desired product (5.35 g, 91%) as brown oil. 1NMR (300 MHz, CDCl3): δ 7.56 (s, 1H), 7.30 (d, J=8.1 Hz, 2H), 7.20 (br.d, 2H), 5.20 (br.s, 0.5H), 4.62 (br.s, 0.5H), 4.39 (br, 2H), 3.86 (s, 3H), 3.74 (s, 3H), 3.27 (m, 2H), 3.08 (m, 2H), 1.62 (m, 2H), 1.50 (br.d, 9H), 1.43 (s, 9H). LCMS (EI) m/z: 501 (M+Na+).

後処理

  1. customwas degassed
  2. additionThe reaction mixture was diluted with EtOAc (500 mL)
  3. washwashed with water (300 mL) and brine (300 mL)
  4. concentrationThe organic solution was concentrated
  5. custompurified by flash chromatography (0%-30% EtOAc in heptane)

出典と根拠

ORDレコード
ord-bdbe27f773c24b9cb91bdbbe3243dc46
出典データセット
uspto-grants-2015_11
特許番号
US09193731B2

反応ノート

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