Triethylamine → 1,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamate

HRID 1486453

反応式

HRID 1486453 の反応式
C(N(CC)CC)C.[C:8]([NH:15][C@H:16]([C:24]([OH:26])=O)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Cl.[CH3:28][NH:29][O:30][CH3:31].CCN=C=NCCCN(C)C>C(Cl)Cl>[CH3:31][O:30][N:29]([CH3:28])[C:24](=[O:26])[C@@H:16]([NH:15][C:8](=[O:9])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

生成物 1

HCID 110559451,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamate収率 81.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Triethyl amine (40 g, 0.4 mol) was added to a suspension of Boc-L-phenylalanine (90 g, 0.34 mol) and N,O-dimethylhydroxylamine hydrochloride (36.5 g, 0.37 mol) in DCM (500 mL) at 0° C. with stirring. The suspension was stirred for 10 min and EDCI (HCl salt, 72 g, 0.37 mol) was added. The suspension was stirred for further 3 hours at 0° C. The mixture was quenched with saturated aqueous NaHCO3 (1 L). The layers were separated, and the aqueous phase was re-extracted with DCM (500 mL×3). The combined organic phases were washed with water (1 L×3), 5% KHSO4 aqueous (1 L×3), saturated aqueous NaHCO3 (1 L×3), and brine (1 L×1), was dried (Na2SO4), and was concentrated to dryness. The crude material was further purified by flash chromatography (silica gel, EtOAc/Hexane=1:1) and afforded (S)-tert-butyl 1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-ylcarbamate (85.1 g, 81% yield) as a white solid. 1H NMR (300 MHz, CDCl3): δ 7.1-57.26 (m, 5H), 5.25 (bs, 1H), 4.95 (m, 1H), 3.63 (s, 3H), 3.14 (s, 3H), 2.83-3.07 (m, 2H), 1.37 (s, 9H).

後処理

  1. stirringThe suspension was stirred for 10 min
  2. stirringThe suspension was stirred for further 3 hours at 0° C
  3. customThe mixture was quenched with saturated aqueous NaHCO3 (1 L)
  4. customThe layers were separated
  5. extractionthe aqueous phase was re-extracted with DCM (500 mL×3)
  6. washThe combined organic phases were washed with water (1 L×3), 5% KHSO4 aqueous (1 L×3), saturated aqueous NaHCO3 (1 L×3), and brine (1 L×1)
  7. dry with materialwas dried (Na2SO4)
  8. concentrationwas concentrated to dryness
  9. customThe crude material was further purified by flash chromatography (silica gel, EtOAc/Hexane=1:1)

出典と根拠

ORDレコード
ord-2316fb25af9f4e3d861e65e47dd191ce
出典データセット
uspto-grants-2016_08
特許番号
US09427479B2

関連ノート

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