Diisopropylethylamine → (S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-2-((tert-butoxycarbonyl)amino)-3-hydroxypropanamido)propanoate

HRID 58789

反応式

HRID 58789 の反応式
[NH2:1][C@@H:2]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:9]=1)[C:3]([O:5][CH3:6])=[O:4].[C:24]([NH:31][C@H:32]([C:35](O)=[O:36])[CH2:33][OH:34])([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O.CCOC(C)=O>[CH2:17]([O:16][C:10]1[CH:9]=[C:8]([CH2:7][C@H:2]([NH:1][C:33](=[O:34])[C@@H:32]([NH:31][C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:35][OH:36])[C:3]([O:5][CH3:6])=[O:4])[CH:13]=[CH:12][C:11]=1[O:14][CH3:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117690774(S)-methyl 2-amino-3-(3-(benzyloxy)-4-methoxyphenyl)propanoate

生成物 1

HCID 117690990(S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-2-((tert-butoxycarbonyl)amino)-3-hydroxypropanamido)propanoate収率 73%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Crude (S)-methyl 2-amino-3-(3-(benzyloxy)-4-methoxyphenyl)propanoate (TFA salt, 12 mmol) was dissolved in DMF (50 mL) followed by addition of Boc-L-serine (2.47 g, 12 mmol), HATU (6.87 g, 18.1 mmol) and DIPEA (10 mL) at 0° C. with stirring. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. EtOAc (200 mL) and water (200 mL) was added and two layers were separated. The aqueous phase was extracted with EtOAc (100 mL×3) and the combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (CH2Cl2/methanol (MeOH)=20:1) to afford (S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-2-((tert-butoxycarbonyl)amino)-3-hydroxypropanamido)propanoate (4.4 g, 73% yield).

後処理

  1. stirringstirred for 3 h
  2. customtwo layers were separated
  3. extractionThe aqueous phase was extracted with EtOAc (100 mL×3)
  4. washthe combined organic phases were washed with brine (200 mL×3)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel (CH2Cl2/methanol (MeOH)=20:1)

出典と根拠

ORDレコード
ord-0ff1ec043eb74049b6781d91b35c38df
出典データセット
uspto-grants-2016_09
特許番号
US09434761B2

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