Citric Acid → HCID 24954055, compound

HRID 2278700Notes

Reaction equation

HRID 2278700 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([NH:13][CH:14]3[CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:15]3)=[CH:10][N:11]=2)[C:6](=[O:23])[C:5]([C:24]([O:26]CC)=[O:25])=[CH:4]1)[CH3:2].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([NH:13][CH:14]3[CH2:15][C:16]4[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:22]3)=[CH:10][N:11]=2)[C:6](=[O:23])[C:5]([C:24]([OH:26])=[O:25])=[CH:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 24954056HCID 24954056, compound

Product 1

HCID 24954055HCID 24954055, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
52.5 °C

Procedure

Ethanol (42.0 L) was added to reactor at 25-30° C., followed by ethyl 1-ethyl-6-(indan-2-ylamino)-4-oxo-1,8-naphthyridine-3-carboxylate (4.20 kg) with stirring. Aqueous sodium hydroxide solution (prepared by dissolving 3.4 kg of sodium hydroxide into 42.0 L of water) was added to reaction mixture at 25-30° C. and reactor temperature was raised to 50-55° C. The reaction mixture was stirred at 50-55° C. for 2 h and reaction progress was monitored by TLC. After completion of hydrolysis (˜3 h), the reaction mass was, cooled to 25-30° C. and pH was adjusted to 5-6 by addition of citric acid solution (prepared by dissolving 5.2 kg of citric acid in 47.0 L of water). The reaction mass was stirred for 20-25 minutes at 25-30° C. and filtered, the solid mass was washed with water (42.0 L) and acetone (21.0 L). The material was transferred to drying trays and dried with hot-air dryer at 70-75° C. until the water content decreased to 1.0%, yielding the desired compound (90%) as a solid. 1H NMR (DMSO-d6, 500 MHz): 1.40(3H, t, J=7.0 Hz), 2.86-2.90(2H, m), 3.37-3.41(2H, m), 4.38(1H, d, J=5.5 Hz), 4.62 (2H, q, J=7.0 Hz), 7.06(1H, d, J=6.0 Hz), 7.17-7.18(2H, m), 7.26-7.27(2H, m), 7.60(1H, d, J=2.5 Hz), 8.52(1H, d, J=2.0 Hz), 9.00 (1H, s), 15.30(1H, s). 13C NMR (DMSO-d6, 125 MHz): 15.19, 46.92, 52.92, 107.12, 109.42, 121.58, 124.63, 126.41, 140.11, 141.12, 143.33, 143.43, 145.93, 166.12, 177.53.

Workup

  1. stirringThe reaction mixture was stirred at 50-55° C. for 2 h
  2. customreaction progress
  3. customAfter completion of hydrolysis (˜3 h)
  4. temperaturecooled to 25-30° C.
  5. stirringThe reaction mass was stirred for 20-25 minutes at 25-30° C.
  6. filtrationfiltered
  7. washthe solid mass was washed with water (42.0 L) and acetone (21.0 L)
  8. customto drying trays
  9. dry with materialdried with hot-air dryer at 70-75° C. until the water content

Sources & evidence

ORD record
ord-4adc28c429034a05a6d421ab7df9a0d0
Source dataset
uspto-grants-2015_09
Patent number
US09133188B2

Reaction notes

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