Triethylamine → 1-(3,4-Difluorobenzoyl)azetidine

HRID 20519

Reaction equation

HRID 20519 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][C:16]=1[F:17])[C:11]([OH:13])=O.Cl.[NH:19]1[CH2:22][CH2:21][CH2:20]1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[F:7][C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][C:16]=1[F:17])[C:11]([N:19]1[CH2:22][CH2:21][CH2:20]1)=[O:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 991663,4-Difluorobenzoic acidHCID 12308726Azetidine hydrochloride

Product 1

HCID 593468591-(3,4-Difluorobenzoyl)azetidineYield 50.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (1.05 mL, 12.0 mmol) was added to a solution of 3,4-difluorobenzoic acid (1.58 g, 10 mmol) in DCM (50 mL) containing DMF (1 drop). The reaction was stirred at ambient temperature for 16 h then evaporated to dryness. The residue was redissolved in DCM (25 mL) and azetidine hydrochloride (1.12 g, 12.0 mmol) added followed by triethylamine (4.18 mL, 30.0 mmol). The mixture was stirred at ambient temperature for 2 h then concentrated in vacuo. The residue was partitioned between ethyl acetate and 1N hydrochloric acid, the organic phase washed with a saturated aqueous solution of sodium bicarbonate followed by brine, dried (MgSO4), and concentrated in vacuo. The title compound was crystallized from an ethyl acetate/hexane mixture to give a white crystalline solid (1.0 g).

Workup

  1. customthen evaporated to dryness
  2. dissolutionThe residue was redissolved in DCM (25 mL)
  3. stirringThe mixture was stirred at ambient temperature for 2 h
  4. concentrationthen concentrated in vacuo
  5. customThe residue was partitioned between ethyl acetate and 1N hydrochloric acid
  6. washthe organic phase washed with a saturated aqueous solution of sodium bicarbonate
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe title compound was crystallized from an ethyl acetate/hexane mixture

Sources & evidence

ORD record
ord-35f62b13bbf54e95be508ca62a2d14d2
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Linked notes

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