HCID 89922359, compound → HCID 89923237, compound

HRID 921806Notes

Reaction equation

HRID 921806 reaction equation
[Cl:1][C:2]1[C:9]([N+:10]([O-])=O)=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:13][CH2:14][C@@H:15]1[CH2:20][O:19][CH2:18][CH2:17][N:16]1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[O:30][CH3:31]>CO.ClCCl.[Cl-].[NH4+].[Zn]>[NH2:10][C:9]1[CH:8]=[C:5]([CH:4]=[C:3]([O:13][CH2:14][C@@H:15]2[CH2:20][O:19][CH2:18][CH2:17][N:16]2[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=2[O:30][CH3:31])[C:2]=1[Cl:1])[C:6]#[N:7]

Participants

6

Reactant 1

HCID 89922359HCID 89922359, compound

Product 1

HCID 89923237HCID 89923237, compoundYield 77.8%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalyst2×HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent2×

Procedure

Zinc (107 mg, 1.630 mmol) was added to a mixture of (S)-4-chloro-3-((4-(2,4-dimethoxybenzyl)morpholin-3-yl)methoxy)-5-nitrobenzonitrile (isomer B, 73 mg, 0.163 mmol) and ammonium chloride (174 mg, 3.26 mmol) in methanol (5 mL) and the reaction mixture was stirred at room temperature for 2 hours. More zinc (107 mg, 1.630 mmol) was added and stirring continued until reactions complete. The reaction mixture was diluted with dichloromethane and ammonium chloride precipitated. Solids were filtered and the filtrate was concentrated. The residue was partitioned between dichloromethane and saturated sodium bicarbonate. The layers were separated and aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (12 g column, eluting with 5-35% ethyl acetate/hexanes) to give (S)-3-amino-4-chloro-5-((4-(2,4-dimethoxybenzyl)morpholin-3-yl)methoxy)benzonitrile (53 mg) as a oil.

Workup

  1. stirringstirring
  2. customprecipitated
  3. filtrationSolids were filtered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was partitioned between dichloromethane and saturated sodium bicarbonate
  6. customThe layers were separated
  7. extractionaqueous layer was extracted with dichloromethane two more times
  8. dry with materialThe combined organic layers were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customthe crude product was purified by flash chromatography on silica gel using
  12. washan automated ISCO system (12 g column, eluting with 5-35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a660327692dd47668a3ba0d13c6b49b7
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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