4-Methylmorpholine → Z-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-OPh

HRID 462868

反応式

HRID 462868 の反応式
[NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:10]([NH:12][C@H:13]([C:21]([NH:23][C@H:24]([C:37]([O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:38])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:22])[C@@H:14]([CH3:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].S(O)(C1C=CC(C)=CC=1)(=O)=O.O.[NH:68]([C:77]([O:79][CH2:80][C:81]1[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=1)=[O:78])[C@H:69]([C:74]([OH:76])=O)[C@H:70]([CH2:72][CH3:73])[CH3:71].CN1CCOCC1.ClC(OCC(C)C)=O>CN(C=O)C.[Pd]>[C:40]1([O:39][C:37](=[O:38])[C@H:24]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])[NH:23][C:21](=[O:22])[C@H:13]([C@@H:14]([CH3:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[NH:12][C:10](=[O:11])[C@H:2]([C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6])[NH:1][C:74](=[O:76])[C@H:69]([C@H:70]([CH2:72][CH3:73])[CH3:71])[NH:68][C:77]([O:79][CH2:80][C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)=[O:78])[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

参加物

8

反応物 5

HCID 79724-Methylmorpholine2 回HCID 62365Isobutyl chloroformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 2724772N-[(Phenylmethoxy)carbonyl]-L-isoleucineHCID 18597979HCID 18597979、化合物

生成物 1

HCID 131714167Z-Ile-Thr(tBu)-Thr(tBu)-Lys(Boc)-OPh

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 6228Dimethylformamide溶媒3 回

反応条件

温度
-35 °C

実験手順

A solution of Z-Thr(tBu)-Thr(tBu)-Lys(Boc)-OPh (346.9 g, 450 mmol) in 1 l DMF was hydrogenated in the presence of Tos-OH.H2O (85.6 g, 450 mmol) and 10% Pd-C. After the hydrogenation was completed the catalyst was filtered off. Z-Ile-OH (132.66, 500 mmol) was dissolved in 700 ml DMF and cooled to -35° C. While stirring at -35° C., N-methylmorpholine (55 ml, 500 mmol) was added, followed by the addition of isobutyl chloroformate (65 ml, 500 mmol). The reaction mixture was activated for 5 min. at -15° C. and quickly cooled to -20° C. The precooled DMF solution (-25° C.) from the hydrogenation step and N-methylmorpholine (50 ml, 450 mmol) were added simultaneously. The reaction mixture was stirred for 15 min. at -15° C. and 1 h at 25° C. and evaporated in vacuo. The residue was dissolved in 3 l ethyl acetate and washed with 10% Na2CO3 sol. (2×1.5 l), satd. NaCl-sol. (1×1 l), 5% KHSO4 /10% K2SO4 sol. (2×1.5 l) and satd. NaCl-sol., dried over Na2SO4, filtered and evaporated in vacuo. The residue was crystallized from ethyl acetate (2 l)/ether (2 l).

後処理

  1. filtrationwas filtered off
  2. temperaturequickly cooled to -20° C
  3. stirringThe reaction mixture was stirred for 15 min. at -15° C. and 1 h at 25° C.
  4. customevaporated in vacuo
  5. dissolutionThe residue was dissolved in 3 l ethyl acetate
  6. washwashed with 10% Na2CO3 sol. (2×1.5 l)
  7. dry with material, dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue was crystallized from ethyl acetate (2 l)/ether (2 l)

出典と根拠

ORDレコード
ord-e0f771f3113e41d09fd3de357d05a8bc
出典データセット
uspto-grants-1985_05
特許番号
US04517119

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