Chloroacetic Acid → 5-Chloromethyl-4-(3-fluoro-phenyl)-[1,2,4]oxadiazole

HRID 1710413Notes

Reaction equation

HRID 1710413 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)C(NO)=N.[Cl:12][CH2:13][C:14]([OH:16])=O.Cl.C([N:20]=[C:21]=[N:22]CCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[Cl:12][CH2:13][CH:14]1[O:16][N:20]=[CH:21][N:22]1[C:4]1[CH:9]=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=1

Participants

7

Reactant 4

HCID 300Chloroacetic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178513300HCID 178513300, compound

Product 1

HCID 685026525-Chloromethyl-4-(3-fluoro-phenyl)-[1,2,4]oxadiazoleYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

3-Fluoro-N-hydroxy-benzamidine (1.4 g, 9.08 mmol), chloroacetic acid (0.94 g, 9.99 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.91 g, 9.99 mmol) and 1-hydroxybenzotriazole hydrate (1.35 g, 9.99 mmol) were mixed in N,N-dimethylformamide (15 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (50 mL), washed with water (50 mL), washed with aqueous saturated sodium bicarbonate (75 mL), washed with water again (50 mL) and washed with brine (50 mL). The organic phase was dried over sodium sulfate and concentrated to give a solid. The solid was dissolved in N,N-dimethylformamide (10 mL) and the reaction mixture stirred at 120° C. for 1.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), washed with water (3×50 mL) and washed with brine (50 mL). The organic phase was dried over sodium sulfate and concentrated. The residue was purified on silica gel eluting with 10 to 30% ethyl acetate in hexanes to give the product as a yellow oil (1.15 g, 60%). 1H NMR (300 MHz, CDCl3): δ 7.91 (dd, 1H), 7.82 (m, 1H), 7.5 (m, 1H), 7.25 (m, 1H), 4.78 (s, 2H).

Workup

  1. washwashed with water (50 mL)
  2. washwashed with aqueous saturated sodium bicarbonate (75 mL)
  3. washwashed with water again (50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto give a solid
  8. stirringthe reaction mixture stirred at 120° C. for 1.5 hours
  9. temperatureThe reaction mixture was cooled to room temperature
  10. washwashed with water (3×50 mL)
  11. washwashed with brine (50 mL)
  12. dry with materialThe organic phase was dried over sodium sulfate
  13. concentrationconcentrated
  14. customThe residue was purified on silica gel eluting with 10 to 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b7b1a90c02d64443a06d3374db76b72d
Source dataset
uspto-grants-2010_09
Patent number
US07790717B2

Reaction notes

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