4-Methylmorpholine → HCID 54318947、化合物

HRID 963685ノート

反応式

HRID 963685 の反応式
[Br-].[C:2]1([P+:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:9][C:10]#[N:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N([CH2:29][CH3:30])CC)C.[C:31]([O:35][C:36]([NH:38][C@H:39]([C:51](O)=[O:52])[CH:40](CC1C=CC=CC=1)C(O)=O)=[O:37])([CH3:34])([CH3:33])[CH3:32].[CH3:54]N1CCOCC1.[CH2:61]([O:65][C:66](Cl)=[O:67])[CH:62]([CH3:64])[CH3:63].C(C[PH4])#N>C1COCC1>[CH2:61]([O:65][C:66](=[O:67])[CH2:40][CH:39]([NH:38][C:36]([O:35][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:37])[C:51](=[O:52])[C:9]([C:10]#[N:11])=[P:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:62]1[CH:64]=[CH:30][CH:29]=[CH:54][CH:63]=1

参加物

8

反応物 6

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 11811037(Cyanomethyl)triphenylphosphonium bromideHCID 14032956HCID 14032956、化合物HCID 178511461HCID 178511461、化合物

生成物 1

HCID 54318947HCID 54318947、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a suspension of triphenyl cyanomethyl phosphonium bromide (1, 0.68 g, 1.8 mmol) in anhydrous THF (10 mL) cooled in an ice bath was added triethylamine (396 mg, 546 μL, 3.9 mmol) and the mixture stirred in an ice bath for 15 min. To a solution of N-t-butyloxycarbonyl-β-benzylaspartic acid (2, 575 mg, 1.8 mmol) in THF (15 mL) cooled to -15° C. was added N-methyl morpholine (180 mg, 196 μL, 1.8 mmol) followed by iso-butylchloroformate (243 mg, 231 μL, 1.8 mmol). The resulting solution was stirred at -15° C. for 5 min before being added dropwise with stirring to the previously prepared cyanomethylphosphorane solution. The mixture was stirred at 0° C. for 15 min and then allowed to warm to room temperature and then stirred for a further 16 h. The precipitate was removed by filtration and the solvent removed under reduced pressure. The mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane) to yield the product as a clear oil which solidified on drying (0.76 g, 70%): mp 42°-44° C.; 1H NMR (CDCl3) δ1.39 (s, 9H, Boc CH3 's), 2.99 (d, 2H, β--CH2), 5.06 (m, 3H, α--CH & benzyl CH2), 5.62 (d, 1H, NH), 7.28 (m, 5H, benzyl aromatic CH's), 7.52 (m, 15H, PPh3 aromatic CH's); MS (EI, calculated for C36 H35N2O5P, 606.2284) m/e 606.2292 (M+).

後処理

  1. temperaturecooled in an ice bath
  2. stirringThe resulting solution was stirred at -15° C. for 5 min
  3. additionbefore being added dropwise
  4. stirringThe mixture was stirred at 0° C. for 15 min
  5. stirringstirred for a further 16 h
  6. customThe precipitate was removed by filtration
  7. customthe solvent removed under reduced pressure
  8. customThe mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-2e5665cdb28043da96aed536a7efe5c6
出典データセット
uspto-grants-1998_06
特許番号
US05763576

反応ノート

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