Hydrochloric Acid → HCID 131717768, compound

HRID 2082226Notes

Reaction equation

HRID 2082226 reaction equation
[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([C:19](O)=[O:20])[CH2:3][C:4]1[N:8]=[CH:7][N:6]([S:9]([C:12]2[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:5]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:45][C@@H:46]([C:59]([NH:61][C@H:62]([C:70]([O:72][CH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1)=[O:71])[CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)=[O:60])[CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[N:50]([CH:57]=[O:58])[CH:49]=1>C(Cl)Cl.CN(C=O)C>[NH:1]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[C@H:2]([C:19]([NH:45][C@@H:46]([C:59]([NH:61][C@H:62]([C:70]([O:72][CH2:73][C:74]1[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=1)=[O:71])[CH2:63][C:64]1[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=1)=[O:60])[CH2:47][C:48]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[N:50]([CH:57]=[O:58])[CH:49]=1)=[O:20])[CH2:3][C:4]1[N:8]=[CH:7][N:6]([S:9]([C:12]2[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 6455010Boc-His(Tos)-OHHCID 15755292HCID 15755292, compound

Product 1

HCID 131717768HCID 131717768, compoundYield 83.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of Boc-His(Tos)-OH (0.81 g) in methylene chloride (10 ml) were added NMM (0.22 ml) and isobutyl chloroformate (0.26 ml) successively at -15° C., and the mixture was stirred for ten minutes. On the other hand, a solution of HCl.H-D-Trp(CHO)-Phe-OBzl (1.00 g) in DMF (20 ml) was cooled at -30° C. and thereto was added NMM (0.22 ml). This solution was added to the above mentioned mixture and stirred for two hours at -30° C. After evaporation and extraction with ethyl acetate, the organic layer was washed successively with 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water and saturated sodium chloride solution, and dried over magnesium sulfate. After evaporation, the residue was subjected to column chromatography on silica gel (100 g) and eluted with a mixture of chloroform and methanol (100:1). The fractions containing the object compound were combined and evaporated. The residue was pulverized with n-hexane, filtered, washed with n-hexane and dried to give Boc-His(Tos)-D-Trp(CHO)-Phe-OBzl (1.42 g).

Workup

  1. additionThis solution was added to the
  2. stirringstirred for two hours at -30° C
  3. customAfter evaporation and extraction with ethyl acetate
  4. washthe organic layer was washed successively with 2% hydrochloric acid, water, 2% sodium hydrogencarbonate, water and saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customAfter evaporation
  7. washeluted with a mixture of chloroform and methanol (100:1)
  8. additionThe fractions containing the object compound
  9. customevaporated
  10. filtrationfiltered
  11. washwashed with n-hexane
  12. customdried

Sources & evidence

ORD record
ord-ae2f0ada253f49368f792f299db2c0d5
Source dataset
uspto-grants-1993_02
Patent number
US05187156

Reaction notes

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