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

HRID 1774367Notes

Reaction equation

HRID 1774367 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 98.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 2-chloro-4-fluoropyridine (1.26 g, 9.58 mmol) and 4-amino-1-naphthol hydrochloride (750 mg, 3.83 mmol) in NMP (40 mL) at −20° C. was added potassium tert-butoxide (1.29 g, 11.50 mmol) and the reaction mixture then warmed to RT for 2.5 hr. The mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL and 2×80 mL) and 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 and the volatiles were removed in vacuo to give 4-(2-chloropyridin-4-yloxy)naphthalen-1-amine as a brown solid (1.02 g, 92%): m/z 271 (M+H)+ (ES+).

Workup

  1. extractionextracted with EtOAc (100 mL and 2×80 mL)
  2. washthe combined organic extracts were washed with brine (150 mL)
  3. customdried
  4. customevaporated in vacuo
  5. customthe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-0367dc1f83b14a8988cb0ac161b09be7
Source dataset
uspto-grants-2016_02
Patent number
US09260410B2

Reaction notes

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