Acetonitrile → HCID 86755903, compound

HRID 366036Notes

Reaction equation

HRID 366036 reaction equation
C([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([C:32]([NH:34][C@@H:35]([C:37]1[CH:42]=[CH:41][C:40]([Br:43])=[CH:39][CH:38]=1)[CH3:36])=[O:33])[NH:16][C:17](=[O:31])[CH:18]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(OCC1C=CC=CC=1)=O.C(#N)C.C[Si](I)(C)C>C(Cl)Cl>[C:19]1([CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:17]([NH:16][C@H:15]([C:32]([NH:34][C@@H:35]([C:37]2[CH:42]=[CH:41][C:40]([Br:43])=[CH:39][CH:38]=2)[CH3:36])=[O:33])[CH2:14][CH2:13][CH2:12][NH2:11])=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 85247Trimethylsilyl iodideHCID 86755904HCID 86755904, compound

Product 1

HCID 86755903HCID 86755903, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(R)-N5 -(Cbz)-N2 -(diphenylacetyl)-(S)-N-[1-(4-bromophenyl)ethyl]ornithine amide (0.50 g; 0.78 mmol; from step (c) above) was suspended in CH2Cl2 :acetonitrile (20 mL; 1:3) and was cooled to 0° C. Trimethylsilyl iodide (0.17 g, 0.86 mmol) was added at 0° C. and the reaction stirred for 2 hours at 0° C. (solids dissolving as the reaction proceeded). When the deprotection was complete, as determined by TLC analysis, the reaction was quenched with water and diluted with EtOAc. The organic layer was separated and washed with water (1×), 1 N sodium thiosulfate (1×) and brine (2×). The combined aqueous washings were extracted with CH2Cl2. The organics were combined and triethylamine (5 mL) was added. The mixture was allowed to stand for 18 hours, transferred to a separating funnel, washed with brine (3×), dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product as a yellow solid (0.40 g). The crude product was chromatographed on silica gel eluting with MeOH:CH2Cl2 (3:7), then MeOH:CH2Cl2 (1:1), to give sub-title compound (free base) as an off-white solid (0.25 g).

Workup

  1. dissolutiondissolving as the reaction
  2. customthe reaction was quenched with water
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with water (1×), 1 N sodium thiosulfate (1×) and brine (2×)
  6. extractionThe combined aqueous washings were extracted with CH2Cl2
  7. additiontriethylamine (5 mL) was added
  8. waitto stand for 18 hours
  9. customtransferred to a separating funnel
  10. washwashed with brine (3×)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give the crude product as a yellow solid (0.40 g)
  15. customThe crude product was chromatographed on silica gel eluting with MeOH:CH2Cl2 (3:7)

Sources & evidence

ORD record
ord-028cfb9a5dd54d27964615e108ffad9c
Source dataset
uspto-grants-2000_10
Patent number
US06127414

Reaction notes

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