Hydrochloric Acid → Methyl 3-amino-2-{[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino}benzoate

HRID 1831014Notes

Reaction equation

HRID 1831014 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]2[C:26]([N+:27]([O-])=O)=[CH:25][CH:24]=[CH:23][C:18]=2[C:19]([O:21][CH3:22])=[O:20])=[CH:11][CH:10]=1)#[N:2].[Sn].Cl.[OH-].[Na+]>O1CCCC1>[NH2:27][C:26]1[C:17]([NH:16][CH2:15][C:12]2[CH:13]=[CH:14][C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[C:1]#[N:2])=[CH:10][CH:11]=2)=[C:18]([CH:23]=[CH:24][CH:25]=1)[C:19]([O:21][CH3:22])=[O:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 5352426Tin atomHCID 15654651Methyl 2-{[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino}-3-nitrobenzoate3×

Product 1

HCID 15654653Methyl 3-amino-2-{[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino}benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
27.5 °C

Procedure

Methyl 2-[[(2′-cyanobiphenyl-4-yl)methyl]amino]-3-nitrobenzoate [MBN] (400 kg) obtained in Reference Example 4(3) and tetrahydrofuran [THF] (1080 kg) were mixed, and the MBN solution was stirred. Tin (400 kg) and 35% hydrochloric acid (1322 kg) were mixed, the mixture was stirred at 25 to 30° C. for about 5 hours, warmed to about 80° C. over about 3 hours, and stirred at about 80° C. for about 8 hours. The resulting stannous chloride solution was added dropwise to the MBN solution at 15 to 25° C. over 5 to 8 hours to carry out reduction reaction at 15 to 25° C. for 2 to 5 hours. After completion of the reaction, the pH of solution was adjusted to 12 with 24% sodium hydroxide (about 2000 L) and flaky sodium hydroxide (about 177 kg). The organic layer was separated, and washed twice with an aqueous sodium bicarbonate solution (950 L) and three times with an aqueous saturated sodium chloride solution (840 L). The organic layer was filtered through a 3μ filter, and the solvent was distilled off. The residue was dissolved in ethyl acetate (540 kg), and concentrated again to give concentrate of methyl 3-amino-2-[[(2′-cyanobiphenyl-4-yl)methyl]animo]benzoate [MBA].

Workup

  1. temperaturewarmed to about 80° C. over about 3 hours
  2. stirringstirred at about 80° C. for about 8 hours
  3. customreduction reaction at 15 to 25° C. for 2 to 5 hours
  4. customAfter completion of the reaction
  5. customThe organic layer was separated
  6. washwashed twice with an aqueous sodium bicarbonate solution (950 L) and three times with an aqueous saturated sodium chloride solution (840 L)
  7. filtrationThe organic layer was filtered through a 3μ filter
  8. distillationthe solvent was distilled off
  9. dissolutionThe residue was dissolved in ethyl acetate (540 kg)
  10. concentrationconcentrated again
  11. customto give
  12. concentrationconcentrate of methyl 3-amino-2-[[(2′-cyanobiphenyl-4-yl)methyl]animo]benzoate [MBA]

Sources & evidence

ORD record
ord-c1778ef65fcf4118b65fd3b3f40cc566
Source dataset
uspto-grants-2006_06
Patent number
US07067546B2

Reaction notes

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