Dichloromethane → HCID 54445607, compound

HRID 2379459Notes

Reaction equation

HRID 2379459 reaction equation
C([NH:8][C@H:9]([C:14]([OH:16])=[O:15])[CH2:10][CH2:11][CH2:12][NH2:13])(OC(C)(C)C)=O.F[C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[C:20]#[N:21].C(Cl)Cl>C(O)C.[OH-].[Na+]>[NH2:8][C@@H:9]([CH2:10][CH2:11][CH2:12][NH:13][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[C:20]#[N:21])[C:14]([OH:16])=[O:15]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 678552-Fluorobenzonitrile2×HCID 7018784(2S)-5-amino-2-{[(tert-butoxy)carbonyl]amino}pentanoic acid

Product 1

HCID 54445607HCID 54445607, compoundYield 2.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 14798Sodium HydroxideSolvent2×

Procedure

A solution of 928 mg (4 mmoles) of Nα -Boc-L-ornithine and 968 mg (8 mmoles) of 2-fluorobenzonitrile in 4 mL of ethanol and 4 mL of 1N NaOH were heated at reflux for 24 hours. Another 8 mmoles each of 1N NaOH and 2-fluorobenzonitrile were then added and reflux was continued for another 24 hours. The clear solution was cooled to room temperature, and the white paste dumped into 125 mL of CH2Cl2 and extracted with 100 mL of water made basic (pH 12) with NaOH. The aqueous extract was acidified with 5N HCl, and extracted with 125 mL of CH2Cl2. The organic phase was washed with 1M HCl, dried (Na2SO4) and concentrated in vacuo to give an oil. The oil was purified by flash chromatography on silica gel, eluting with 2:1 ethyl acetate:ethanol containing 1% triethylamine. The sole fluorescent product was an oil, 132 mg (10%), with rf of 0.49 in the elution solvent. 125 mg of the oil was dissolved in 22 mL of 5:1:1 acetic acid/water/12M HCl, and stirred for 3 hours at room temperature. The sample was concentrated in vacuo, then ethanol was added and the sample again concentrated in vacuo to give a waxy solid. This was recrystallized from water to give 22.5 mg of white needles. The mother liquor yielded 67 mg of white foam on concentration. Yield (100%).: mp >265°; MS (FAB) m/e calc'd for C12H10N3O2 : 234.1243, found 234.1231; M/Z 223 (M+), 224 (M+H)+. 1H NMR (300 MHz, D2O) δ: 1.74 (m, 2H), 1.96 (m, 2H), 3.33 (t, J=6.0 Hz, 2H), 3.79 (t, J=5.8 Hz, 1H), 6.71 (t, J=7 Hz, 1H), 6.92 (d, J=9 Hz, 1H), 7.55 (m, 1H).

Workup

  1. temperatureat reflux for 24 hours
  2. temperaturereflux
  3. extractionextracted with 100 mL of water
  4. extractionThe aqueous extract
  5. extractionextracted with 125 mL of CH2Cl2
  6. washThe organic phase was washed with 1M HCl
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto give an oil
  10. customThe oil was purified by flash chromatography on silica gel
  11. washeluting with 2:1 ethyl acetate
  12. dissolution125 mg of the oil was dissolved in 22 mL of 5:1:1 acetic acid/water/12M HCl
  13. concentrationThe sample was concentrated in vacuo
  14. additionethanol was added
  15. concentrationthe sample again concentrated in vacuo
  16. customto give a waxy solid
  17. customThis was recrystallized from water

Sources & evidence

ORD record
ord-99faacc7e35c421396cc3641a7a117f2
Source dataset
uspto-grants-1994_11
Patent number
US05362747

Reaction notes

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