Lithium Hydroxide → 1-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide

HRID 1865719ノート

反応式

HRID 1865719 の反応式
O.[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([OH:7])=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:53]/[C:54](=[CH:60]\[C@@H:61]([N:65]([CH3:74])[C:66](=[O:73])[C@H:67]([C:69]([CH3:72])([CH3:71])[CH3:70])[NH2:68])[CH:62]([CH3:64])[CH3:63])/[C:55]([O:57]CC)=[O:56].[OH-].[Li+]>ClCCl.CO.ClCCl.O.O1CCCC1.O>[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([NH:68][C@H:67]([C:66]([N:65]([C@@H:61]([CH:62]([CH3:64])[CH3:63])/[CH:60]=[C:54](/[C:55]([OH:57])=[O:56])\[CH3:53])[CH3:74])=[O:73])[C:69]([CH3:71])([CH3:72])[CH3:70])=[O:7]

参加物

11

反応物 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 162119581-Methyl-L-proline--water (1/1)

生成物 1

HCID 115963751-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide収率 28%

試薬・触媒・溶媒 5

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 21908982Water methylene chloride溶媒

実験手順

To a solution of N-methyl-L-proline monohydrate (0.26 g, 1.79 mmol) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.4 g, 2.69 mmol) in anhydrous dichloromethane (3.0 ml) at 25° C. is added diisopropylethylamine (0.63 ml, 3.62 mmol) under an inert atmosphere. To this solution is added a solution of ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.39 g, 1.27 mmol, WO 99/32509) in anhydrous dichloromethane (2.0 ml). The resulting reaction mixture is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo. The residue (300 mg, 0.78 mmol) is dissolved in methanol (6.85 ml), water (1.8 ml) and tetrahydrofuran (3.25 ml). To this reaction mixture is added aqueous lithium hydroxide solution (3.54 ml, 3.54 mol) The resulting mixture is stirred at room temperature overnight. The reaction mixture is diluted with dichloromethane/water. The organic layer is washed with citric acid, brine, dried over sodium sulfate and filtered. The solvent is removed in vacuo, and the residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile) to give the product as a yellow oil, 0.08 g (28% yield). MS: m/z 396.28 (M+1)

後処理

  1. customThe resulting reaction mixture
  2. customThe reaction mixture is evaporated in vacuo
  3. stirringis stirred at room temperature overnight
  4. washThe organic layer is washed with citric acid, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent is removed in vacuo
  8. customthe residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile)

出典と根拠

ORDレコード
ord-d3dcd8dbf5dc4e9887bcbea06143be5d
出典データセット
uspto-grants-2009_12
特許番号
US07626023B2

反応ノート

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