1,2-Dichloroethane → (S)-2-Amino-1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-butan-1-one

HRID 1830133Notes

Reaction equation

HRID 1830133 reaction equation
C(OC([NH:8][CH:9]([CH2:15][CH3:16])[CH:10]([OH:14])[C:11]([OH:13])=O)=O)(C)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O[NH:32][C:33](=[NH:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CN1CCOCC1.C1C2C(C3ON=C(N)N=3)CN(C2)C1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C@@H:9]([CH2:15][CH3:16])[C:10]([C:11]1[O:13][N:40]=[C:33]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:32]=1)=[O:14]

Participants

9

Reactant 7

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1639383-(3-Amino-1,2,4-oxadiazol-5-yl)-1-azabicyclo(2.2.1)heptaneHCID 219627633-{[(Tert-butoxy)carbonyl]amino}-2-hydroxypentanoic acidHCID 178513281HCID 178513281, compound

Product 1

HCID 58649533(S)-2-Amino-1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-butan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid (500 mg, 2.14 mmol) was combined with EDC (600 mg, 3.14 mmol), HOBt (600 mg, 3.92 mmol), and N-hydroxy-benzamidine (292 mg, 2.14 mmol). Dichloromethyl (10 mL) was added and then 4-methylmorpholine (1 mL). The mixture was stirred at ambient temperature for 16 hours. After dilution with ethyl acetate (200 mL), the solution was washed with water (30 mL), saturated aqueous NaHCO3 solution and brine, dried with MgSO4 and evaporated under vacuum. The crude product was dissolved in pyridine (10 mL) and heated at 80° C. for 15 hours. The pyridine was evaporated under vacuum and the residue was purified by flash chromatography on silica gel (eluent: ethyl acetate) to yield 290 mg (0.83 mmol). The oxadiazole (145 mg, 0.41 mmol) was dissolved in CH2Cl2 (4 mL) and TFA (4 mL) was added. After stirring for 1 hour, the mixture was evaporated to dryness to yield (S)-2-Amino-1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-butan-1-one.

Workup

  1. additionDichloromethyl (10 mL) was added
  2. washAfter dilution with ethyl acetate (200 mL), the solution was washed with water (30 mL), saturated aqueous NaHCO3 solution and brine
  3. dry with materialdried with MgSO4
  4. customevaporated under vacuum
  5. dissolutionThe crude product was dissolved in pyridine (10 mL)
  6. temperatureheated at 80° C. for 15 hours
  7. customThe pyridine was evaporated under vacuum
  8. customthe residue was purified by flash chromatography on silica gel (eluent: ethyl acetate)
  9. customto yield 290 mg (0.83 mmol)
  10. stirringAfter stirring for 1 hour
  11. customthe mixture was evaporated to dryness

Sources & evidence

ORD record
ord-e95ceaa41ab94fafbd85a0f59689b464
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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