Sodium Bicarbonate → (S)-5-((((2-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)pentanoic acid

HRID 1482353Notes

Reaction equation

HRID 1482353 reaction equation
[C:1](=[O:23])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]=[N+:11]=[N-:12].[NH:24]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:25]([C:30]([OH:32])=[O:31])[CH2:26][CH2:27][CH2:28][NH2:29].C(=O)(O)[O-].[Na+].S(=O)(=O)(O)[O-].[K+]>O1CCOCC1.C(OCC)(=O)C.O>[N:10]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH2:3][O:2][C:1]([NH:29][CH2:28][CH2:27][CH2:26][C@H:25]([NH:24][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:30]([OH:32])=[O:31])=[O:23])=[N+:11]=[N-:12]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 516920Potassium bisulfateHCID 7018784(2S)-5-amino-2-{[(tert-butoxy)carbonyl]amino}pentanoic acidHCID 89668497HCID 89668497, compound

Product 1

HCID 89668621(S)-5-((((2-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)pentanoic acidYield 102.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Azidobenzyl (4-nitrophenyl) carbonate (Compound tk13) (458 mg, 1.459 mmol) was added to a suspension of Boc-Orn-OH (Compound tk56) (308 mg, 1.326 mmol) and sodium bicarbonate (278 mg, 3.32 mmol) in 1,4-dioxane (3 mL)-water (2 mL). The reaction mixture was stirred at room temperature for 20.25 hours and then cooled in an ice bath and diluted with ethyl acetate and water, and a saturated aqueous potassium bisulfate solution (1.5 mL) was added to the resulting mixture. The mixture was extracted with ethyl acetate (×2), and the organic phase was washed with water (10 mL×2) and brine (10 mL) and dried over sodium sulfate. Following concentration under reduced pressure, the resulting crude product was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate) to afford (S)-5-((((2-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)pentanoic acid (Compound tk61) (556.0 mg, quant.).

Workup

  1. temperaturecooled in an ice bath
  2. extractionThe mixture was extracted with ethyl acetate (×2)
  3. washthe organic phase was washed with water (10 mL×2) and brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentration under reduced pressure
  6. customthe resulting crude product was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-ce0eba71f6f44238975779f83ceb4b43
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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