Ammonium Chloride → Methyl 2-(5-(4-aminophenyl)thiazole-2-carboxamido)-3-methylbutanoate

HRID 1024431

Reaction equation

HRID 1024431 reaction equation
[Cl-].[NH4+].[CH3:3][CH:4]([CH3:27])[CH:5]([NH:10][C:11]([C:13]1[S:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][CH:19]=2)=[CH:16][N:17]=1)=[O:12])[C:6]([O:8][CH3:9])=[O:7]>CCO.C1COCC1.O.[Fe]>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([C:15]2[S:14][C:13]([C:11]([NH:10][CH:5]([CH:4]([CH3:27])[CH3:3])[C:6]([O:8][CH3:9])=[O:7])=[O:12])=[N:17][CH:16]=2)=[CH:19][CH:20]=1

Participants

7

Reactant 2

HCID 25517Ammonium ChlorideHCID 67150324Methyl 3-methyl-2-(5-(4-nitrophenyl)thiazole-2-carboxamido)butanoate2×

Product 1

HCID 67150329Methyl 2-(5-(4-aminophenyl)thiazole-2-carboxamido)-3-methylbutanoateYield 92.3%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Ammonium chloride (1.04 g) and iron (777 mg) were added to a solution of Methyl 3-methyl-2-(5-(4-nitrophenyl)thiazole-2-carboxamido)butanoate (Intermediate 2, step C, 2.15 g) in EtOH (21.5 ml), THF (8.6 ml), and Water (8.6 ml). The reaction mixture was refluxed at 80° C. for 3 hours. It was then cooled, filtered through celite and the solvent was removed under reduced pressure to get dark brown residue. The residue was taken in water and extracted with ethyl acetate. The organic layer was separated, dried over Na2SO4 and concentrated to get dark brown residue which was purified by column on silica gel in 2.5:7.5 EtOAc:chloroform to get yellow sticky solid which was crystallized in DCM/pet ether to yield 1.82 g (91%) of the title compound. 1HNMR (DMSO-d6, 300 MHz): δ 8.59 (d, 1H), 8.15 (s, 1H), 7.42 (d, 2H), 6.63 (d, 2H), 5.76 (bs, 2H), 4.31 (m, 1H), 3.67 (s, 3H), 2.27 (m, 1H), 0.91 (d, 6H); MS (ES+): m/z 334 (M+1).

Workup

  1. temperatureIt was then cooled
  2. filtrationfiltered through celite
  3. customthe solvent was removed under reduced pressure
  4. customto get dark brown residue
  5. extractionextracted with ethyl acetate
  6. customThe organic layer was separated
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto get dark brown residue which
  10. customwas purified by column on silica gel in 2.5:7.5 EtOAc
  11. customchloroform to get yellow sticky solid which
  12. customwas crystallized in DCM/pet ether

Sources & evidence

ORD record
ord-daf9ccc5ba91423eab22caed2f04b704
Source dataset
uspto-grants-2014_05
Patent number
US08722901B2

Linked notes

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