Methyl iodide → Boc-N-methyl-D-Valine

HRID 1518774ノート

反応式

HRID 1518774 の反応式
[NH:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4].[CH3:16]I.[H-].[Na+]>C1COCC1.C(OCC)C>[C:12]([O:11][C:9]([N:1]([CH3:16])[C@H:2]([CH:3]([CH3:5])[CH3:4])[C:6]([OH:8])=[O:7])=[O:10])([CH3:13])([CH3:15])[CH3:14]

参加物

6

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acid

生成物 1

HCID 7018800Boc-N-methyl-D-Valine収率 100.6%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of N-Boc-D-Val-OH (1.0 g, 4.60 mmol) in THF (15.3 mL) at 0° C. was added MeI (2.88 mL, 46.0 mmol, 10.0 equiv). NaH (60%, 1.84 g, 46.0 mmol, 10.0 equiv) was added as a solid to the suspension over a period of 2 hours. After stirring for 12 hours at room temperature, the reaction mixture was diluted with diethyl ether and quenched with water slowly. Aqueous layer was extracted with diethyl ether followed by acidified to pH 3 with 10% citric acid and extraction with ethyl acetate. Combined organic layer was washed with brine, dried with Na2SO4, filtered and concentrated in vacuo to afford compound 3.3a (1.07 g) which was used for the next step without further purification. MS m/z (M+Na) 254.2. 1H NMR (400 MHz, CDCl3) 4.02-4.17 (m, 1H), 2.88 (s, 3H), 2.40-2.14 (m, 1H), 1.54-1.39 (m, 9H), 1.03 (d, J=6.60 Hz, 3H), 0.92 (d, J=6.70 Hz, 3H).

後処理

  1. customquenched with water slowly
  2. extractionAqueous layer was extracted with diethyl ether
  3. extractionby acidified to pH 3 with 10% citric acid and extraction with ethyl acetate
  4. washCombined organic layer was washed with brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-f411adeb265447efa36923cacea8d82d
出典データセット
uspto-grants-2015_07
特許番号
US09072696B2

反応ノート

読み込み中…