Ammonium Hydroxide → HCID 89544977, compound

HRID 2283395Notes

Reaction equation

HRID 2283395 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C@@H:8]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([C:18]([C:20]2[CH:25]=[CH:24][C:23](Br)=[CH:22][N:21]=2)=[O:19])[C:12]=1[F:27])[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].[OH-].[NH4+:30]>CN1C(=O)CCC1.[Cu-]=O>[C:1]([O:5][C:6](=[O:28])[NH:7][C@@H:8]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([NH2:30])=[CH:22][N:21]=2)=[O:19])[C:12]=1[F:27])[CH2:9][CH3:10])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 89544773HCID 89544773, compound

Product 1

HCID 89544977HCID 89544977, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

Step 2 To a solution of {(R)-1-[3-(5-bromo-pyridine-2-carbonyl)-4-chloro-2-fluoro-phenyl]-propyl}-carbamic acid tert-butyl ester (371 mg, 0.79 mmol) in NMP (2 mL) was added copper (I) oxide (23 mg, 0.16 mmol, 0.2 eq.) and ammonium hydroxide (˜29% in water, 2 mL) in a Reacti-vial and the mixture heated at 80° C. for 4 h. The mixture was partitioned between EtOAc (20 mL) and water (20 mL) and the organic phase extracted with further EtOAc (10 mL). Combined organic phase was washed with water (3×20 mL) and brine (10 mL) before it was dried (MgSO4), filtered and concentrated. Purified by silica column, 25 M, eluting 25-80% EtOAc in petrol to give {(R)-1-[3-(5-amino-pyridine-2-carbonyl)-4-chloro-2-fluoro-phenyl]-propyl}-carbamic acid tert-butyl ester (226 mg, 0.55 mmol, 70%). [M+H]+ 408

Workup

  1. customThe mixture was partitioned between EtOAc (20 mL) and water (20 mL)
  2. extractionthe organic phase extracted with further EtOAc (10 mL)
  3. washCombined organic phase was washed with water (3×20 mL) and brine (10 mL) before it
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurified by silica column, 25 M
  8. washeluting 25-80% EtOAc in petrol

Sources & evidence

ORD record
ord-94592012ec5648faafc3a90260616614
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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