2-Morpholinoethanol → 3-Amino-7-methoxy-6-(2-morpholin-4-yl-ethoxy)-naphthalene-2-carboxylic acid tert-butyl ester

HRID 902412Notes

Reaction equation

HRID 902412 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:17]([NH2:18])=[CH:16][C:15]2[C:10](=[CH:11][C:12]([O:20][CH3:21])=[C:13]([OH:19])[CH:14]=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C1(P(C2C=CC=CC=2)C2C=CC=CN=2)C=CC=CC=1>O1CCCC1>[C:1]([O:5][C:6]([C:8]1[C:17]([NH2:18])=[CH:16][C:15]2[C:10](=[CH:11][C:12]([O:20][CH3:21])=[C:13]([O:19][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:14]=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 611632-MorpholinoethanolHCID 6218932-PyridyldiphenylphosphineHCID 120627383-Amino-6-hydroxy-7-methoxynaphthalene-2-carboxylic acid tert-butyl ester

Product 1

HCID 120627393-Amino-7-methoxy-6-(2-morpholin-4-yl-ethoxy)-naphthalene-2-carboxylic acid tert-butyl esterYield 69.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.72 g (2.49 mmol) of 3-amino-6-hydroxy-7-methoxy-naphthalene-2-carboxylic acid tert-butyl ester in 7.5 ml of tetrahydrofuran is added 0.46 mL (3.74 mmol) of 4-(2-hydroxyethyl)morpholine, followed by the addition of 1.34 g (4.98 mmol) of diphenyl-2-pyridylphosphine and 0.6 mL (3.87 mmol) of diethyl azadicarboxylate. The resulting mixture is stirred at room temperature for 1.5 hours, quenched with water, diluted with ethyl acetate and the two layers are separated. The organic layer is extracted with 0.2N hydrochloric acid. After neutralizing the aqueous layer with a saturated solution of sodium bicarbonate, it is extracted with ethyl acetate. The ethyl acetate extract is dried over anhydrous sodium sulfate, filtered and evaporated to yield a brown oil. The oil is purified by silica gel chromatography, utilizing a gradient of ethyl acetate/hexane (85:15 to 100:0), to give 0.7 g of 3-amino-7-methoxy-6-(2-morpholin-4-yl-ethoxy)-naphthalene-2-carboxylic acid tert-butyl ester as an orange solid, mp 125-127° C.

Workup

  1. customquenched with water
  2. additiondiluted with ethyl acetate
  3. customthe two layers are separated
  4. extractionThe organic layer is extracted with 0.2N hydrochloric acid
  5. extractionis extracted with ethyl acetate
  6. extractionThe ethyl acetate extract
  7. dry with materialis dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a brown oil
  11. customThe oil is purified by silica gel chromatography

Sources & evidence

ORD record
ord-b2d5fd5c4a3246cb9bea4dfff87db23d
Source dataset
uspto-grants-2008_04
Patent number
US07365197B2

Reaction notes

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