Hydrochloric Acid → 6-(3-Chloro-4-fluorobenzyl)-4-methoxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylic acid

HRID 18010Notes

Reaction equation

HRID 18010 reaction equation
C([O:4][C:5]1[N:6]=[C:7]([C:27]([O:29]CC)=[O:28])[C:8]2[CH2:9][CH2:10][N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=3)[C:12](=[O:17])[C:13]=2[C:14]=1[O:15][CH3:16])(=O)C.O.[OH-].[Li+].O.Cl>C(O)C>[Cl:26][C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][C:22]=1[F:25])[CH2:18][N:11]1[CH2:10][CH2:9][C:8]2[C:13](=[C:14]([O:15][CH3:16])[C:5](=[O:4])[NH:6][C:7]=2[C:27]([OH:29])=[O:28])[C:12]1=[O:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 59455606Ethyl 3-(acetyloxy)-6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Product 1

HCID 594556036-(3-Chloro-4-fluorobenzyl)-4-methoxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl 3-(acetyloxy)-6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (217 g, 0.48 mol), lithium hydroxide monohydrate (70.7 g, 1.67 mol), and water (320 mL) in ethanol (1.8 L) was sonicated for 20 minutes. The reaction mixture was cooled in an ice-water bath and treated with hydrochloric acid (425 mL, 3 M). The resultant light yellow solid was filtered, washed successively with water (1 L), a 3:2 v/v mixture of water and ethanol (500 mL), MTBE (750 mL), and air dried. The yellow solid was dissolved in anhydrous DMF (700 mL) and concentrated under vacuum. The procedure was repeated twice to remove residual water. The yellow solid was triturated with MTBE, filtered, and stored under vacuum overnight to afford the title acid.

Workup

  1. customwas sonicated for 20 minutes
  2. temperatureThe reaction mixture was cooled in an ice-water bath
  3. filtrationThe resultant light yellow solid was filtered
  4. washwashed successively with water (1 L)
  5. additiona 3:2 v/v mixture of water and ethanol (500 mL), MTBE (750 mL), and air
  6. customdried
  7. dissolutionThe yellow solid was dissolved in anhydrous DMF (700 mL)
  8. concentrationconcentrated under vacuum
  9. customto remove residual water
  10. customThe yellow solid was triturated with MTBE
  11. filtrationfiltered
  12. customstored under vacuum overnight

Sources & evidence

ORD record
ord-207290e1df2e497ba910aec51a369ef0
Source dataset
uspto-grants-2010_06
Patent number
US07741315B2

Reaction notes

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