Trifluoroacetic acid → Bis-boc-l-ornithyl-d-homophenylalanine quinoline-3-amide

HRID 1365890Notes

Reaction equation

HRID 1365890 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.Cl[C:32]([O:34]CC)=[O:33].[N:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[C:39]([C:47]([NH2:49])=[O:48])[CH:38]=1.[C:50](N[C@@H](C(O)=O)CCC1C=CC=CC=1)(OC(C)(C)C)=[O:51].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[N:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[C:39]([C:47]([NH2:49])=[O:48])[CH:38]=1.[C:1]([N:8]([C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[C@H:9]([C:50]([NH:49][C@@H:47]([C:32]([OH:34])=[O:33])[CH2:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[O:51])[CH2:10][CH2:11][CH2:12][NH2:13])([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2×HCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 18638603Di-boc-ornithineHCID 66963140N-Boc-D-Homophenylalanine Quinoline-3-amide

Product 1

HCID 131728705Bis-boc-l-ornithyl-d-homophenylalanine quinoline-3-amideYield 136.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of NaNd-bis-Boc-L-Ornithine (2.79 g, 8.4 mmol), triethylamine (1.29 mL, 9.2 mmol) and methylene chloride (90 mL) was stirred at 25° C. for 10 min, cooled to −10° C. and treated with ethyl chloroformate (0.80 mL, 8.4 mmol). The mixture was stirred at −10° C. for 2 hrs. During this time N-Boc-D-Homophenylalanine Quinoline-3-amide (2.27 g, 5.6 mmol) was treated with trifluoroacetic acid (15 mL) at 25° C. for 1 hr. The solution was concentrated to dryness and treated with diethyl ether (10 mL). The solid was filtered and dried. It was suspended in methylene chloride (40 mL) and neutralized with triethylamine (1.6 mL, 11.2 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. It was purified by column chromatography on silica gel (ethyl acetate:hexane=2:1) to give the title compound (2.55 g) as white solid.

Workup

  1. concentrationThe solution was concentrated to dryness
  2. additiontreated with diethyl ether (10 mL)
  3. filtrationThe solid was filtered
  4. customdried
  5. temperatureto warm up to 25° C.
  6. stirringstirred for an additional 1 hr
  7. washthe organic layer was washed with water (30 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customto afford crude product
  12. customIt was purified by column chromatography on silica gel (ethyl acetate:hexane=2:1)

Sources & evidence

ORD record
ord-832d45df92a1423bbc2cd9bbdd78d0b5
Source dataset
uspto-grants-2011_02
Patent number
US07893020B2

Reaction notes

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