Acetic Acid → 4-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-one

HRID 1095787Notes

Reaction equation

HRID 1095787 reaction equation
C([O-])(=O)C.[NH4+:5].[CH:6]1([CH2:9][O:10][C:11]2[C:12]([O:23][CH3:24])=[CH:13][CH:14]=[C:15]3[C:20]=2[NH:19][C:18](=[O:21])[CH:17]=[C:16]3O)[CH2:8][CH2:7]1.C(O)(=O)C>C1(C)C=CC=CC=1>[NH2:5][C:16]1[C:15]2[C:20](=[C:11]([O:10][CH2:9][CH:6]3[CH2:8][CH2:7]3)[C:12]([O:23][CH3:24])=[CH:13][CH:14]=2)[NH:19][C:18](=[O:21])[CH:17]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 517165Ammonium AcetateHCID 573636778-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-one

Product 1

HCID 592681194-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-oneYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Ammonium acetate (620 g, 8.0 mol) was added to a solution of 8-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-one (105 g, 0.40 mol), acetic acid (400 mL), and toluene (200 mL). The reaction was refluxed with a Dean-Stark apparatus for 2 h, and then the mixture was concentrated to remove the toluene. The reaction was then refluxed overnight. Water/ice (200 mL) was added, and with external cooling, the pH was adjusted to 14 using 40% KOH. The resulting solids were collected by filtration and then purified by silica gel chromatography (100:1→30:1; dichloromethane/methanol) to give 75 g of 4-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-one as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.20 (s, 1H), 7.59 (d, 1H), 6.88 (d, 1H), 6.53 (s, 2H), 5.29 (s, 1H), 3.86 (s, 3H), 3.81 (d, 2H), 1.22 (m, 1H), 0.44 (m, 2H), 0.22 (m, 2H); MS (ESI): 261.1.

Workup

  1. temperatureThe reaction was refluxed with a Dean-Stark apparatus for 2 h
  2. concentrationthe mixture was concentrated
  3. customto remove the toluene
  4. temperatureThe reaction was then refluxed overnight
  5. additionWater/ice (200 mL) was added
  6. filtrationThe resulting solids were collected by filtration
  7. custompurified by silica gel chromatography (100:1→30:1; dichloromethane/methanol)

Sources & evidence

ORD record
ord-3d717f43968841ec831de40b79068177
Source dataset
uspto-grants-2012_03
Patent number
US08138205B2

Reaction notes

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