Chlorosuccinimide → HCID 86707797, compound

HRID 2174387Notes

Reaction equation

HRID 2174387 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:8][N:7]([C:9]2[CH:14]=[CH:13][C:12]([CH:15]=[N:16][OH:17])=[CH:11][CH:10]=2)[CH2:6]1)=[O:4].[Cl:18]N1C(=O)CCC1=O.C(=O)([O-])O.[K+].[Cl:31][C:32]1[CH:37]=[C:36]([C:38]([C:40]([F:43])([F:42])[F:41])=[CH2:39])[CH:35]=[C:34]([Cl:44])[C:33]=1[Cl:45]>CN(C=O)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:8][N:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:39][C:38]([C:36]4[CH:37]=[C:32]([Cl:31])[C:33]([Cl:45])=[C:34]([Cl:44])[CH:35]=4)([C:40]([F:42])([F:43])[F:41])[O:17][N:16]=3)=[CH:11][C:10]=2[Cl:18])[CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 31398ChlorosuccinimideHCID 516893Potassium BicarbonateHCID 498201551,2,3-Trichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 867077943-Azetidinecarboxylic acid, 1-[4-[(hydroxyimino)methyl]phenyl]-, methyl ester

Product 1

HCID 86707797HCID 86707797, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of 1-[4-(hydroxyimino-methyl)-phenyl]-azetidine-3-carboxylic acid methyl ester (Preparation 10, 0.95 g, 4.059 mmol, 1 eq.) in DMF (10 mL) was added N-chloro succinimide (0.59 g, 4.46 mmol) at room temperature. Resulting reaction mixture was stirred at 45° C. for 30 minutes. After complete consumption of starting material to chloro intermediate, reaction mixture was cooled to room temperature, potassium hydrogen carbonate (0.61 g, 6.089 mmol) was added followed by of 1,2,3-trichloro-5-(1-trifluoromethyl-vinyl)-benzene (1.33 g, 4.87 mmol) at room temperature. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After consumption of chloro intermediate, reaction mixture was quenched with ice cold water (250 mL) and extracted with EtOAc (2×200 mL). Combined organic layer was dried over anhydrous sodium sulphate and concentrated in vacuo to 1 g crude. Crude compound was purified by column chromatography (silica gel, 100-200 mesh) to afford 0.850 g impure product. Impure product was repurified by column chromatography (silica gel, 100-200 mesh) to afford 0.55 g. 1H NMR (400 MHz, CDCl3): 3.51-3.55 (m, 1H), 3.60 (d, 1H, J=17.08 Hz), 3.75 (s, 3H), 4.0 (d, 1H, J=17.04 Hz), 4.28 (t, 2H, J=7.2 Hz), 4.36 (t, 2H, J=8.36 Hz), 6.45 (d, 1H, J=8.6 Hz), 7.41 (dd, 1H, J1=1.92 Hz, J2=8.6 Hz), 7.46 (d, 1H, J=1.88 Hz), 7.62 (s, 2H); LC-MS (M+H): =542.50.

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material
  4. customto chloro intermediate, reaction mixture
  5. temperaturewas cooled to room temperature
  6. customResulting
  7. customreaction mixture
  8. stirringwas stirred at room temperature for 18 hours under nitrogen atmosphere
  9. customAfter consumption of chloro intermediate, reaction mixture
  10. customwas quenched with ice cold water (250 mL)
  11. extractionextracted with EtOAc (2×200 mL)
  12. dry with materialCombined organic layer was dried over anhydrous sodium sulphate
  13. concentrationconcentrated in vacuo to 1 g crude
  14. customCrude compound was purified by column chromatography (silica gel, 100-200 mesh)

Sources & evidence

ORD record
ord-2fe2e59a7f0442299ff452272eac2992
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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