Hydrochloric Acid → Fmoc-D-Lys(Boc)-D-Lys(Boc)-Leu-Leu-OH

HRID 537628Notes

Reaction equation

HRID 537628 reaction equation
[NH:1]([C:57]([O:59][CH2:60][CH:61]1[C:73]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=2)[C:67]2[C:62]1=[CH:63][CH:64]=[CH:65][CH:66]=2)=[O:58])[C@@H:2]([C:15]([NH:17][C@@H:18]([C:31]([NH:33][C@H:34]([C:39]([NH:41][C@H:42]([C:47]([O:49]CC1C=CC=CC=1)=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[O:40])[CH2:35][CH:36]([CH3:38])[CH3:37])=[O:32])[CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].C(=O)([O-])O.[Na+].Cl>C(Cl)(Cl)Cl.CCCCCCC.FC(F)(F)C(O)=O>[NH:1]([C:57]([O:59][CH2:60][CH:61]1[C:62]2[C:67](=[CH:66][CH:65]=[CH:64][CH:63]=2)[C:68]2[C:73]1=[CH:72][CH:71]=[CH:70][CH:69]=2)=[O:58])[C@@H:2]([C:15]([NH:17][C@@H:18]([C:31]([NH:33][C@H:34]([C:39]([NH:41][C@H:42]([C:47]([OH:49])=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[O:40])[CH2:35][CH:36]([CH3:38])[CH3:37])=[O:32])[CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:16])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 131731956Fmoc-D-Lys(Boc)-D-Lys(Boc)-Leu-Leu-OBzl

Product 1

HCID 131731958Fmoc-D-Lys(Boc)-D-Lys(Boc)-Leu-Leu-OHYield 93%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolvent2×HCID 6422Trifluoroacetic acidSolventHCID 8900HeptaneSolvent

Conditions

Temperature
12.5 °C

Procedure

The crude crystals (1.23 g) of Fmoc-D-Lys(Boc)-D-Lys(Boc)-Leu-Leu-OBzl (2-MeO-4-OC12OC22) were dissolved in a mixture of chloroform (12 mL) and heptane (12 mL), and 3% trifluoroacetic acid/(chloroform-heptane=1:1) solution was added dropwise under ice-cooling. The reaction mixture was stirred in a water bath at 10-15° C. for 3 hr, and 2.5% aqueous sodium hydrogen carbonate solution (18 mL) and chloroform (18 mL) were added. 0.1N Hydrochloric acid was added, and the aqueous layer was adjusted to pH 2. The aqueous layer was removed, and the organic layer was washed 3 times with purified water (10 mL). The combined organic layers were concentrated under reduced pressure, and heptane (30 mL) was added to the residue. The precipitated crystals were washed at 40° C. and collected by filtration to give Fmoc-D-Lys(Boc)-D-Lys(Boc)-Leu-Leu-OH (800 mg, 93%).

Workup

  1. additionwas added dropwise under ice-
  2. temperaturecooling
  3. customThe aqueous layer was removed
  4. washthe organic layer was washed 3 times with purified water (10 mL)
  5. concentrationThe combined organic layers were concentrated under reduced pressure, and heptane (30 mL)
  6. additionwas added to the residue
  7. washThe precipitated crystals were washed at 40° C.
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-820ea2c44316473b8c27c63d2d9eb66b
Source dataset
uspto-grants-2014_10
Patent number
US08859732B2

Reaction notes

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