Phosgene → HCID 10130834, compound

HRID 2307225Notes

Reaction equation

HRID 2307225 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:11][N:10](C(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:9]2)=[CH:4][CH:3]=1.[C:25](Cl)(Cl)=[O:26]>ClCCl.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][N:10]([C:25]([NH:10][CH2:9][C:8]#[CH:5])=[O:26])[CH2:11]2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 6371PhosgeneHCID 22605396HCID 22605396, compound

Product 1

HCID 10130834HCID 10130834, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-(4fluorophenyl)-1-(diphenylmethyl)azetidine (17) (0.38 g) in dichloromethane (5 mL) at 0° C. was added dropwise a solution of 20% phosgene in toluene (1.4 mL). The mixture was stirred for 90 minutes then concentrated in vacuo. To the concentrate was added dichloromethane (5 mL) and to this solution at 0° C. was added, dropwise, with stirring propargylaminc (0.3 mL). The mixture was stirred for 18 hrs at room temperature, diluted with dichworomethane (20 mL), washed (water, brine), dried (Na2SO4) and concentrated in vacuo. The crude material was purified by flash column chromatography (50% ethyl acetate hexane) and then crystallised from diisopropyl ether to give 3-(4-fluoropenyl)-N-(2-propynyl)azetidine-1-carboxamide (19) (0.14 g), m.p. 141° C. (diisopropyl ether). Found: C, 67.32; H, 5.65; N, 11.93. C13Hi3FN2O requires C, 67.23; H, 5.64; N, 12.06%.

Workup

  1. concentrationthen concentrated in vacuo
  2. additionTo the concentrate was added dichloromethane (5 mL)
  3. additionto this solution at 0° C. was added
  4. stirringdropwise, with stirring propargylaminc (0.3 mL)
  5. stirringThe mixture was stirred for 18 hrs at room temperature
  6. additiondiluted with dichworomethane (20 mL)
  7. washwashed (water, brine)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by flash column chromatography (50% ethyl acetate hexane)
  11. customcrystallised from diisopropyl ether

Sources & evidence

ORD record
ord-1b497fa2ea5b4d46b04f4ef22c33106f
Source dataset
uspto-grants-2004_12
Patent number
US06831078B1

Reaction notes

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