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

HRID 2069074Notes

Reaction equation

HRID 2069074 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.[K].[O-]CCCC>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

7

Reactant 4

HCID 27238584-Amino-1-naphthol hydrochlorideHCID 27827922-Chloro-4-fluoropyridineHCID 5462222PotassiumHCID 12476378Butan-1-olate

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 (2a) (750 mg, 3.83 mmol) in NMP (40 mL), at −20° C., was added potassium tart-butoxide (1.290 g, 11.50 mmol). The reaction mixture was allowed to warm to RT and 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 and the solvent was removed in vacuo to give the title compound (72) (1.02 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. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-898f0978a7c2400fb1473a9830c9983a
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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