Diisopropylethylamine → (1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

HRID 1171950

反応式

HRID 1171950 の反応式
Cl.[CH2:2]([O:4][C:5]([C@@:7]1([NH:12][C:13]([C@@H:15]2[CH2:19][C@@H:18]([OH:20])[CH2:17][NH:16]2)=[O:14])[CH2:9][C@H:8]1[CH:10]=[CH2:11])=[O:6])[CH3:3].[CH2:21]([O:24][CH2:25][CH2:26][CH2:27][C@H:28]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:29](O)=[O:30])[CH:22]=[CH2:23].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>C1(C)C=CC=CC=1.C(#N)C.O.C(OCC)(=O)C>[CH2:21]([O:24][CH2:25][CH2:26][CH2:27][C@H:28]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:29]([N:16]1[CH2:17][C@H:18]([OH:20])[CH2:19][C@H:15]1[C:13]([NH:12][C@:7]1([C:5]([O:4][CH2:2][CH3:3])=[O:6])[CH2:9][C@H:8]1[CH:10]=[CH2:11])=[O:14])=[O:30])[CH:22]=[CH2:23]

参加物

9

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21080138N-Boc-5-(2-propen-1-yloxy)-L-norvalineHCID 67330424(1R,2S)-ethyl 1-((3R,5S)-3-hydroxypyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride

生成物 1

HCID 70295348(1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(1R,2S)-ethyl-1-((2S,4R)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride salt (WO2005095403) (2.44 g, 7.76 mmol), (S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)-pentanoic acid (WO2004094452) (2.02 g, 7.39 mmol) and HATU (3.09 g, 8.13 mmol) in toluene (36 mL) and ACN (4 mL) was added DIEA (2.58 mL, 14.78 mmol) at 0° C. The reaction warmed to rt and stirred at rt for 1 hr. Ethyl acetate (30 mL) and water (20 mL) was added. The organic layer was separated and washed with brine, dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Ethyl acetate) to give (1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate as white wax solid (3.55 g, 92%). MS: Calcd.: 523; Found: [M+H]+ 524.

後処理

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of solvent
  5. customthe residue was purified by chromatography (Ethyl acetate)

出典と根拠

ORDレコード
ord-94e0e623d53c406f99a91d69fa890b26
出典データセット
uspto-grants-2010_11
特許番号
US07829665B2

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