Ethyl Acetate → HCID 57692600、化合物

HRID 1511564ノート

反応式

HRID 1511564 の反応式
C[C@@:2]1([C:27]([O-:29])=[O:28])[CH2:6][C@@H:5]([O:7][C:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3Br)[CH2:11]2)=[O:9])[CH2:4][N:3]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].[CH3:30][C:31]([CH3:46])([CH3:45])[C@@H:32]([C:42]([OH:44])=[O:43])[NH:33][C:34]([O:36][CH2:37][CH2:38][CH2:39][C:40]#[CH:41])=[O:35].[C:47]([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1.N1CCCC1.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:23]([O:22][C:20]([N:3]1[C@H:2]([C:27]([O:29][CH3:47])=[O:28])[CH2:6][C@@H:5]([O:7][C:8]([N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[C:41]#[C:40][CH2:39][CH2:38][CH2:37][O:36][C:34]([NH:33][C@H:32]([C:42]([OH:44])=[O:43])[C:31]([CH3:46])([CH3:45])[CH3:30])=[O:35])[CH2:11]2)=[O:9])[CH2:4]1)=[O:21])([CH3:25])([CH3:24])[CH3:26]

参加物

9

反応物 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 574311933-Methyl-N-{[(pent-4-yn-1-yl)oxy]carbonyl}-L-valineHCID 86610193HCID 86610193、化合物

生成物 1

HCID 57692600HCID 57692600、化合物収率 99%

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒HCID 31268Pyrrolidine溶媒

反応条件

温度
70 °C

実験手順

A solution of 1-tert-butyl 2-methyl-(2S,4R)-4-{[(4-bromo-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate (100 mg, 0.21 mmol) and 3-methyl-N-[(pent-4-yn-1-yloxy)carbonyl]-L-valine (103 mg, 0.43 mmol) in THF (1 mL) and pyrrolidine (1 mL) was purged with nitrogen. Copper iodide (4 mg, 0.02 mmol) and Pd(PPh3)4 (25 mg, 0.02 mmol) were added and the reaction mixture was heated for 30 min at 70° C. under nitrogen. The resulting mixture was poured into saturated aqueous NaHCO3 and EtOAc, the organic layer separated and washed twice with 10% citric acid solution, then brine and dried over Na2SO4. The residue was purified by column chromatography on silica gel (eluting with 90:10:1 DCM:MeOH:NH4OH) and concentrated to give N-[({5-[2-({[(3R,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidin-3-yl]oxy}carbonyl)-2,3-dihydro-1H-isoindol-4-yl]pent-4-yn-1-yl}oxy)carbonyl]-3-methyl-L-valine (131 mg, 99% yield) as colorless oil. LRMS (ESI) m/z 530.5 [(M+H)+; calcd for C27H36N3O8: 530.6].

後処理

  1. customthe organic layer separated
  2. washwashed twice with 10% citric acid solution
  3. dry with materialbrine and dried over Na2SO4
  4. customThe residue was purified by column chromatography on silica gel (eluting with 90:10:1 DCM:MeOH:NH4OH)
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-64109b2799bf4528ae69d5c8ec813278
出典データセット
uspto-grants-2012_07
特許番号
US08216999B2

反応ノート

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