Sodium Iodide → (2-((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-ylcarbamoyl)-4-methoxypyridin-3-yloxy)methyl acetate

HRID 75740

反応式

HRID 75740 の反応式
[C:1]([O:4][CH2:5]Br)(=[O:3])[CH3:2].[CH2:7]([C@@H:14]1[C@@H:22]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C@H:21]([CH3:28])[O:20][C:19](=[O:29])[C@@H:18]([NH:30][C:31](=[O:41])[C:32]2[C:37]([OH:38])=[C:36]([O:39][CH3:40])[CH:35]=[CH:34][N:33]=2)[CH2:17][O:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[C:1]([O:4][CH2:5][O:38][C:37]1[C:32]([C:31](=[O:41])[NH:30][C@H:18]2[CH2:17][O:16][CH2:15][C@H:14]([CH2:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C@@H:22]([O:23][CH2:24][CH:25]([CH3:26])[CH3:27])[C@H:21]([CH3:28])[O:20][C:19]2=[O:29])=[N:33][CH:34]=[CH:35][C:36]=1[O:39][CH3:40])(=[O:3])[CH3:2]

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 68536Bromomethyl acetateHCID 86701233N-((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide

生成物 1

HCID 71813198(2-((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-ylcarbamoyl)-4-methoxypyridin-3-yloxy)methyl acetate収率 53%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒2 回

反応条件

温度
50 °C

実験手順

Bromomethyl acetate (48 uL, 0.49 mmol) was added to a suspension of N-((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (160 mg, 0.33 mmol), sodium iodide (NaI, 2.5 mg, 0.02 mmol) and sodium carbonate (Na2CO3; 56 mg, 0.53 mmol) in acetone (3 mL). The mixture was heated to 50° C. and stirred overnight. The suspension was diluted with acetone and filtered. The yellow solution was concentrated and purified by flash chromatography (50% EtOAc in hexanes) to furnish the product as a white foam (97 mg, 53%): IR (film) 3370, 3025, 2957, 2874, 1752, 1677 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=8.2 Hz, 1H), 8.27 (d, J=5.4 Hz, 1H), 7.34-7.23 (m, 2H), 7.20 (dd, J=7.2, 4.8 Hz, 3H), 6.95 (d, J=5.4 Hz, 1H), 5.80-5.64 (m, 2H), 5.13-4.92 (m, 2H), 4.02 (dd, J=11.7, 7.4 Hz, 1H), 3.90 (s, 3H), 3.54-3.28 (m, 5H), 3.14 (dd, J=11.7, 6.4 Hz, 2H), 2.40-2.23 (m, 1H), 2.06 (s, 3H), 2.01-1.82 (m, 2H), 1.50 (d, J=6.4 Hz, 3H), 0.93 (d, J=6.7 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 171.81, 170.31, 163.18, 160.20, 145.79, 143.93, 142.15, 140.02, 129.21 (2), 128.44 (2), 126.10, 109.69, 89.41, 84.58, 79.26, 75.74, 72.34, 72.16, 56.19, 51.81, 47.45, 35.09, 29.19, 20.88, 19.50 (2), 18.83; ESIMS m/z 560.36 ([M+H]+).

後処理

  1. filtrationfiltered
  2. concentrationThe yellow solution was concentrated
  3. custompurified by flash chromatography (50% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-82ea162ae680495a87c2464aead3b6a5
出典データセット
uspto-grants-2014_09
特許番号
US08835462B2

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