Potassium Carbonate → 4-(2-Morpholinoethoxy)naphthalen-1-amine

HRID 1016526Notes

Reaction equation

HRID 1016526 reaction equation
Cl.[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([OH:13])=[CH:5][CH:4]=1.C([Li])CCC.C(OC(NC1C2C(=CC=CC=2)C(O)=CC=1)=O)(C)(C)C.Cl.Cl[CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C1COCC1>[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[CH:5][CH:4]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 27238584-Amino-1-naphthol hydrochlorideHCID 10923237tert-Butyl (4-hydroxynaphthalen-1-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 110439124-(2-Morpholinoethoxy)naphthalen-1-amine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Amino-1-naphthol hydrochloride (40) can be neutralized with a base, such as n-butyl lithium, in a non-protic solvent, such as THF, and reacted with di-tert-butyl dicarbonate (BOC)2O) at temperatures between −78-25° C. The product, 4-tert-butyloxycarbonylamino-1-naphthol (41) can be alkylated with 4-(2-chloroethyl)morpholine hydrochloride in a non-protic solvent, such as acetonitrile, wit a base, such as powdered potassium carbonate, at temperatures between 60-80° C. Purification of the product 4-tert-butyloxycarbonylamino-1-(2-(morpholin-4-yl)ethoxy)naphthalene (42) can be accomplished by silica gel chromatography. Removal of the BOC-protecting group can be accomplished with HCl in a non-protic solvent, such as dioxane, to furnish 1-amino-4-(2-(morpholin-4-yl)ethoxy)naphthalene (39) as the hydrochloride salt.

Workup

  1. custombetween 60-80° C
  2. customPurification of the product 4-tert-butyloxycarbonylamino-1-(2-(morpholin-4-yl)ethoxy)naphthalene (42)
  3. customRemoval of the BOC-

Sources & evidence

ORD record
ord-7bafd865d93647a8a196b20df92bd651
Source dataset
uspto-grants-2002_11
Patent number
US06476023B1

Reaction notes

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