Ammonium Chloride → HCID 67070070, compound

HRID 2390872Notes

Reaction equation

HRID 2390872 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([C:15]2[CH:16]=[C:17]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:18]([O:34][CH3:35])=[C:19]([NH:21][C:22](=[O:33])[C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[C:25]([F:32])[CH:24]=3)[CH:20]=2)=[CH:13][CH:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH4+].[Cl-]>[Fe].CO.O>[NH2:29][C:26]1[CH:27]=[CH:28][C:23]([C:22]([NH:21][C:19]2[CH:20]=[C:15]([C:14]3[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[N:10][CH:11]=[CH:12][CH:13]=3)[CH:16]=[C:17]([C:36]([CH3:38])([CH3:39])[CH3:37])[C:18]=2[O:34][CH3:35])=[O:33])=[CH:24][C:25]=1[F:32]

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 67290880HCID 67290880, compound

Product 1

HCID 67070070HCID 67070070, compoundYield 72.4%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
105 °C

Procedure

step 2—To a suspension of 316 (595 mg, 1.12 mmol) in a 1:1 mixture of MeOH/H2O (4 mL each) at RT was added NH4Cl (601 mg, 11.2 mmol) and iron powder (314 mg, 5.62 mmol). The reaction mixture was warmed to 105° C. and stirred overnight. The reaction was cooled to RT and filtered via Büchner funnel and the filtrate was rinsed with DCM. The filtrate was diluted with H2O and extracted with DCM. The extracts were washed with H2O and brine. The combined aqueous phases were back-extracted with DCM. The combined organic extracts were combined, dried (MgSO4), filtered, and concentrated. The crude residue was purified by SiO2 chromatography, eluting with an EtOAc/hexane gradient (0% to 40% EtOAc) to afford 405 mg (72%) of 4-amino-N-[5-(2-benzyloxy-pyridin-3-yl)-3-tert-butyl-2-methoxy-phenyl]-3-fluoro-benzamide (318) as a foamy, yellow solid.

Workup

  1. temperatureThe reaction was cooled to RT
  2. filtrationfiltered via Büchner funnel
  3. washthe filtrate was rinsed with DCM
  4. additionThe filtrate was diluted with H2O
  5. extractionextracted with DCM
  6. washThe extracts were washed with H2O and brine
  7. extractionThe combined aqueous phases were back-extracted with DCM
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude residue was purified by SiO2 chromatography
  12. washeluting with an EtOAc/hexane gradient (0% to 40% EtOAc)

Sources & evidence

ORD record
ord-d5b3eb274fca4ae3aeb3db03f66f6aaa
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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