Sodium Bicarbonate → 6-Azido-N-(tert-butoxycarbonyl)-L-norleucine

HRID 1482342Notes

Reaction equation

HRID 1482342 reaction equation
C(=O)(O)[O-].[Na+].[NH:6]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:7]([C:13]([OH:15])=[O:14])[CH2:8][CH2:9][CH2:10][CH2:11][NH2:12].Cl.N1(S([N:32]=[N+:33]=[N-])(=O)=O)C=CN=C1.S(=O)(=O)(O)[O-].[K+]>CO.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O>[N:12]([CH2:11][CH2:10][CH2:9][CH2:8][C@H:7]([NH:6][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:13]([OH:15])=[O:14])=[N+:32]=[N-:33]

Participants

8

Reactant 4

HCID 516892Sodium Bicarbonate2×HCID 516920Potassium bisulfateHCID 2733284epsilon-tert-Butyloxycarbonyl-lysineHCID 235839821H-Imidazole-1-sulfonyl azide hydrochloride

Product 1

HCID 251460616-Azido-N-(tert-butoxycarbonyl)-L-norleucineYield 86%

Reagents, catalysts & solvents 3

HCID 24463Copper sulfate pentahydrateCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Sodium bicarbonate (0.65 g, 7.74 mmol) was added to a mixture of Boc-Lys-OH (Compound tk39) (1.0 g, 4.06 mmol) and copper sulfate pentahydrate (20 mg, 0.081 mmol) in methanol (15 mL)-water (3 mL) at room temperature, followed by addition of 1H-imidazole-1-sulfonyl azide hydrochloride synthesized by the method described in the literature (Org. Lett., 2007, 9, 3797) (1.02 g, 4.87 mmol). Sodium bicarbonate (0.65 g, 7.74 mmol) was added to the reaction mixture, followed by stirring at room temperature for 23 hours. The reaction mixture was cooled in an ice bath, followed by addition of a saturated aqueous potassium bisulfate solution (10 mL). The resulting mixture was filtered through celite and washed with ethyl acetate, and the filtrate was then concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (0.05% aqueous trifluoroacetic acid solution/0.05% trifluoroacetic acid-acetonitrile solution) to afford (S)-6-azido-2-((tert-butoxycarbonyl)amino)hexanoic acid (Compound tk48) (948.7 mg, 86%).

Workup

  1. customsynthesized by the method
  2. temperatureThe reaction mixture was cooled in an ice bath
  3. filtrationThe resulting mixture was filtered through celite
  4. washwashed with ethyl acetate
  5. concentrationthe filtrate was then concentrated under reduced pressure
  6. customThe resulting residue was purified by reverse-phase silica gel column chromatography (0.05% aqueous trifluoroacetic acid solution/0.05% trifluoroacetic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-df2565d0a9e548cf8d5dee6fa99884c3
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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