Sulfuric Acid → HCID 13501956, 화합물

HRID 462865

반응식

HRID 462865 반응식
[NH:1]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C@H:2]([C:7]([O:9]N1C(=O)CCC1=O)=O)[CH2:3][CH:4]([CH3:6])[CH3:5].[NH2:27][C@H:28]([C:41]([OH:43])=[O:42])[CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C1CCC(NC2CCCCC2)CC1.OS(O)(=O)=O>CN(C=O)C.C(O)(=O)C.C(N(CC)CC)C>[CH2:20]([O:19][C:17]([NH:1][C@H:2]([C:7]([NH:27][C@H:28]([C:41]([OH:43])=[O:42])[CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])=[O:9])[CH2:3][CH:4]([CH3:5])[CH3:6])=[O:18])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

참가 물질

8

반응물 4

HCID 1118Sulfuric AcidHCID 7582DicyclohexylamineHCID 2733283(2S)-2-amino-6-(((tert-butoxy)carbonyl)amino)hexanoic acid2회HCID 110897513397-35-1

생성물 1

HCID 13501956HCID 13501956, 화합물

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매2회

실험 절차

A solution of Z-Leu-OSu (122.5 g, 0.338 mol) in DMF (1.2 L) was stirred at 0° in a 3 L, 3-necked round bottom flask fitted with a mechanical stirrer and thermometer. The H-Lys(Boc)-OH (83.26 g, 0.338 mol) was added and the solution stirred at 0° for 15 min. Triethylamine (47.6 mL, 0.338 mol) was added and the reaction mixture stirred at 0° for 30 min and 25° for 3 h. Additional triethylamine (20 mL) was added to maintain the pH at 8 and the reaction mixture stirred for an additional 20 h. At the end of this time, tlc showed some unreacted H-Lys(Boc)-OH and the reaction mixture was stirred for an additional 24 h (pH 8). The reaction mixture was cooled (0°), acidified with glacial acetic acid (160 mL) and evaporated in vacuo. The residue (oil) was dissolved in EtOAc (1.5 L) and washed with 1M citric acid (2×600 mL) and 10% NaCl (2×700 mL), dried (MgSO4), filtered and concentrated in vacuo. The oily residue was dissolved in anhydrous ether (4 L) and dicyclohexylamine (70.7 mL) added followed by the addition of 1 L of ether. After standing in the cold room for 72 h, the white salt was collected and dried to yield 210.8 g (90%); m.p. 125°-128° (recrystallization of an analytical sample increased the m.p. to 143°-146°); [α]D25 -4.17 (c 1, MeOH); Rf 0.39 (CHCl3 :MeOH:AcOH; 85:10:5). The free acid was generated from the DCHA salt in the following manner: Z-Leu-Lys(Boc)-OH.DCHA (201.9 g, 0.291 mol) was stirred in EtOAC:0.5N H2SO4 (2 L:727 mL) until all the solid dissolved. The organic layer was separated, washed with 0.5N H2SO4 (730 mL), dried (MgSO4) and evaporated in vacuo. Yield: 150.6 g (100%); [α]D25 +3.38° (c 1, CHCl3); Rf 0.64 (CHCl3 :MeOH:AcOH; 85:10:5).

후처리

  1. customfitted with a mechanical stirrer
  2. stirringthe reaction mixture stirred at 0° for 30 min and 25° for 3 h
  3. temperatureto maintain the pH at 8
  4. stirringthe reaction mixture stirred for an additional 20 h
  5. stirringthe reaction mixture was stirred for an additional 24 h (pH 8)
  6. temperatureThe reaction mixture was cooled (0°)
  7. customevaporated in vacuo
  8. dissolutionThe residue (oil) was dissolved in EtOAc (1.5 L)
  9. washwashed with 1M citric acid (2×600 mL) and 10% NaCl (2×700 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. dissolutionThe oily residue was dissolved in anhydrous ether (4 L)
  14. additiondicyclohexylamine (70.7 mL) added
  15. additionfollowed by the addition of 1 L of ether
  16. waitAfter standing in the cold room for 72 h
  17. customthe white salt was collected
  18. customdried
  19. customto yield 210.8 g (90%)
  20. customm.p. 125°-128° (recrystallization of an analytical sample
  21. temperatureincreased the m.p. to 143°-146°)
  22. customThe organic layer was separated
  23. washwashed with 0.5N H2SO4 (730 mL)
  24. dry with materialdried (MgSO4)
  25. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-7fc04e81c2624e0e8ff41bdee95caf25
출처 데이터셋
uspto-grants-1985_05
특허 번호
US04517119

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