Chlorosuccinimide → 3-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-ethoxycarbonylmethylpyrazinone

HRID 398393Notes

Reaction equation

HRID 398393 reaction equation
[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:12]3[C:13](=[O:24])[N:14]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:15]=[CH:16][N:17]=3)[CH2:9][O:8][CH2:7]2)[CH2:3][CH2:2]1.[Cl:25]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:12]3[C:13](=[O:24])[N:14]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:15]([Cl:25])=[CH:16][N:17]=3)[CH2:9][O:8][CH2:7]2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 700247483-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-1-ethoxycarbonylmethylpyrazinone

Product 1

HCID 700248653-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-6-chloro-1-ethoxycarbonylmethylpyrazinone

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A stirred solution of 3-(trans-3-cyclopropylmethoxytetrahydrofuran-4-ylamino)-1-ethoxycarbonylmethylpyrazinone from step 5 above (1.4 g, 4.15 mmol) and N-chlorosuccinimide (0.61 g, 4.57 mmol) in CHCl3 was heated to reflux for 6 h. More N-chlorosuccinimide (0.11 g, 0.83 mmol) was added and refluxing was continued for an additional 6 h. The reaction was diluted with CHCl3 and washed with aqueous NaHCO3. The organic phase was separated, dried over Mg SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using a gradient elution of 25-50% EtOAc:hexanes to give the title compound as an amorphous solid (1.1 g, TLC Rf=0.5, 1:1 EtOAc:hexanes; HPLC RT=7.97 min, method A).

Workup

  1. temperatureto reflux for 6 h
  2. temperaturerefluxing
  3. washwashed with aqueous NaHCO3
  4. customThe organic phase was separated
  5. dry with materialdried over Mg SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography
  9. washa gradient elution of 25-50% EtOAc

Sources & evidence

ORD record
ord-b48f87ec1eb14304a025e85982e299b1
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

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