4-Amino-1-naphthol hydrochloride → 4-(2-Chloropyridin-4-yloxy)naphthalen-1-amine

HRID 593417Notes

Reaction equation

HRID 593417 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][N:3]=1.Cl.[NH2:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([OH:21])=[CH:13][CH:12]=1.CC(C)([O-])C.[K+]>CN1C(=O)CCC1.O>[Cl:1][C:2]1[CH:7]=[C:6]([O:21][C:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:11]([NH2:10])=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 27238584-Amino-1-naphthol hydrochlorideHCID 27827922-Chloro-4-fluoropyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 585325784-(2-Chloropyridin-4-yloxy)naphthalen-1-amineYield 98.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 2-chloro-4-fluoropyridine (1.261 g, 9.58 mmol) and 4-amino-1-naphthol hydrochloride (2) (750 mg, 3.83 mmol) in NMP (40 mL), at −20° C., was added potassium tert-butoxide (1.290 g, 11.50 mmol). The reaction mixture was allowed to warm to RT. After 2.5 hr, the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL then 2×80 mL). The combined organic extracts were washed with brine (150 mL), dried and evaporated in vacuo. The crude product was subjected to SCX capture and release eluting with 1% NH3 in MeOH solution and the solvent was removed in vacuo to give 4-(2-chloropyridin-4-yloxy)naphthalen-1-amine (3) (1.019 g, 92%) as a brown solid: m/z 271 (M+H)+ (ES+).

Workup

  1. extractionextracted with EtOAc (100 mL
  2. washThe combined organic extracts were washed with brine (150 mL)
  3. customdried
  4. customevaporated in vacuo
  5. washeluting with 1% NH3 in MeOH solution
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-42e991d8b9dc44878d87f222899e3b68
Source dataset
uspto-grants-2016_01
Patent number
US09242960B2

Reaction notes

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