Ammonia → HCID 118276949, compound

HRID 1053699Notes

Reaction equation

HRID 1053699 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:16]([O-:18])=[O:17])=[C:6]([CH:8]2[CH2:13][C:12](=[O:14])[O:11][C:10](=[O:15])[CH2:9]2)[CH:7]=1.[NH3:19]>O1CCCC1.CO>[NH2:19][C:10](=[O:15])[CH2:9][CH:8]([C:6]1[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[N+:16]([O-:18])=[O:17])[CH2:13][C:12]([OH:11])=[O:14]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 118277016HCID 118277016, compound

Product 1

HCID 118276949HCID 118276949, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Adapting literature known protocols (Ji, et al., Tetrahedron Lett., 2009, 50(45), 6166-6168; and Hoekstra, et al., Org. Proc. Dev. Dev., 1997, 1(1), 26-38), 5-amino-3-(5-chloro-2-nitro-phenyl)-5-oxo-pentanoic acid (18d) is prepared from 4-(5-chloro-2-nitro-phenyl)tetrahydropyran-2,6-dione (18a) (2.70 g, 10.0 mmol) in tetrahydrofuran (THF) (20 mL) with a concentrated solution of ammonia (NH3) in methanol (MeOH) (˜7.0 M; about 100 mL) at room temperature for about 14 hours. The reaction course is followed by TLC and/or LC/MS till completion. The reaction mixture is concentrated to dryness under reduced pressure using a rotary evaporator. The residue is triturated with ethyl acetate (EtOAc) (2×). The solids remaining after titruation are acidified at a temperature of about 0° C. (ice bath) with 1.0 M hydrochloric acid. Aqueous work-up yields the title compound (18d). The crude material may either be used directly in the next step or may be further purified by silica gel column chromatography using methanol (MeOH), dichloromethane (DCM), and hexane mixtures or by re-crystallization.

Workup

  1. concentrationThe reaction mixture is concentrated to dryness under reduced pressure
  2. customa rotary evaporator
  3. customThe residue is triturated with ethyl acetate (EtOAc) (2×)
  4. customare acidified at a temperature of about 0° C. (ice bath) with 1.0 M hydrochloric acid

Sources & evidence

ORD record
ord-dff4240023014d639e837be7640afe44
Source dataset
uspto-grants-2016_07
Patent number
US09394236B2

Reaction notes

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