Triethylamine → bis-Boc-L-ornithyl-(3,4,5-trifluoro)-D-Phenylalanine Quinoline-3-amide

HRID 1365894Notes

Reaction equation

HRID 1365894 reaction equation
[C:1]([N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:9](C(O)=O)[CH2:10][CH2:11][CH2:12][NH2:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.ClC([O:34][CH2:35][CH3:36])=O.FC(F)(F)C(O)=[O:40].[N:44]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=[C:46]([C:54]([NH2:56])=[O:55])[CH:45]=1.[F:57][C:58]1[CH:59]=[C:60]([CH:67]=[C:68]([F:71])[C:69]=1[F:70])[CH2:61]C(C(O)=O)N.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(OCC)(=O)C.C(OCC)C>[N:44]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=[C:46]([C:54]([NH2:56])=[O:55])[CH:45]=1.[C:1]([N:8]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C@H:9]([C:54]([NH:56][C@@H:36]([C:35]([OH:34])=[O:40])[CH2:61][C:60]1[CH:67]=[C:68]([F:71])[C:69]([F:70])=[C:58]([F:57])[CH:59]=1)=[O:55])[CH2:10][CH2:11][CH2:12][NH2:13])([O:3][C:4]([CH3:6])([CH3:5])[CH3:7])=[O:2]

Participants

9

Reactant 5

HCID 8471Triethylamine2×HCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 18638603Di-boc-ornithineHCID 87217078(3,4,5-trifluoro)-D,L-phenylalanine Quinoline-3-amide Trifluoroacetate

Product 1

HCID 86602424bis-Boc-L-ornithyl-(3,4,5-trifluoro)-D-Phenylalanine Quinoline-3-amideYield 27.3%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of NaNd-bis-Boc-L-Ornithine (1.25 g, 3.7 mmol), triethylamine (0.57 mL, 4.1 mmol) and methylene chloride (60 mL) was stirred at 25° C. for 10 min, cooled to −10° C. and treated with ethyl chloroformate (0.36 mL, 3.7 mmol). The mixture was stirred at −10° C. for 2 hrs. (3,4,5-trifluoro)-D,L-phenylalanine Quinoline-3-amide Trifluoroacetate (1.31 g) was suspended in methylene chloride (20 mL) and neutralized with triethylamine (0.70 mL, 5.0 mmol). The resultant solution was added dropwise to the mixed anhydride and the mixture was allowed to warm up to 25° C. and stirred for an additional 1 hr. Saturated sodium bicarbonate (30 mL) was added, the organic layer was washed with water (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated to dryness to afford crude product. TLC (silica gel Merck plates, diethyl ether:ethyl acetate=1:1) revealed the presence of two diastereoisomers. They were separated by column chromatography on silica gel with diethyl ether:ethyl acetate=3:1 to give the title compound (0.25 g) as white solid.

Workup

  1. temperatureto warm up to 25° C.
  2. stirringstirred for an additional 1 hr
  3. washthe organic layer was washed with water (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customto afford crude product
  8. customThey were separated by column chromatography on silica gel with diethyl ether

Sources & evidence

ORD record
ord-4255ab7dcbea4bf7870cce39059c63e0
Source dataset
uspto-grants-2011_02
Patent number
US07893020B2

Reaction notes

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