Hydrochloric Acid → 6-Fluoro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic Acid Ethyl Ester

HRID 901253Notes

Reaction equation

HRID 901253 reaction equation
[C:1]([O:9]CC)(=O)[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[F:14][C:15]1[CH:35]=[N:34][C:18]2[N:19]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)C(=O)[O:21][C:22](=O)[C:17]=2[CH:16]=1.Cl>CC(N(C)C)=O>[CH2:6]([O:5][C:3]([C:2]1[C:1](=[O:9])[N:19]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:18]2[C:17]([C:22]=1[OH:21])=[CH:16][C:15]([F:14])=[CH:35][N:34]=2)=[O:4])[CH3:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 596996236-fluoro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione

Product 1

HCID 692163256-Fluoro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic Acid Ethyl EsterYield 98%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Diethyl malonate (10.79 mL, 71.38 mmol) was added slowly to a suspension of NaH (60% in mineral oil, 3.13 g, 78.24 mmol) in dimethylacetamide (200 mL) and stirred at room temperature for 0.5 h under inert atmosphere. 6-Fluoro-1-(4-methoxy-benzyl)-1H-pyrido-[2,3-d]-[1,3]-oxazine-2,4-dione (69) (21.5 g, 71.31 mmol) was added to the solution and heated at 110° C. for 4 h (TLC control). The solution was cooled and poured into ice water. The pH of the solution was adjusted to 3 by cold 10% HCl. The solids formed were filtered, washed by excess water, and dried in a vacuum oven to yield 26.01 g (98%) of 6-fluoro-4-hydroxy-1-(4-methoxy-benzyl)-2-oxo-1,2-dihydro-[1,8]-naphthyridine-3-carboxylic acid ethyl ester (74) as pale yellow solids. MP: 163° C.; 1H-NMR (DMSO-d6): δ 1.27 (t, J=7.2 Hz, 3H), 3.68 (s, 3H), 4.27 (q, J=7.0 Hz, 2H), 5.43 (s, 2H), 6.81 (m, Hz, 2H), 7.19 (m, 2H), 8.26 (dd, J=2.8, 8.0 Hz, 1H), 8.74 (d, J=2.8 Hz, 1H), 13.00 (br. S, 1H); EIMS: 373 (M+1).

Workup

  1. temperatureheated at 110° C. for 4 h (TLC control)
  2. temperatureThe solution was cooled
  3. customThe solids formed
  4. filtrationwere filtered
  5. washwashed by excess water
  6. customdried in a vacuum oven

Sources & evidence

ORD record
ord-d0ac4600f6064efbabf1ef00303a2cc3
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

Loading…