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

HRID 1817334Notes

Reaction equation

HRID 1817334 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[F:28])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:22][CH3:23])[C:10](=[O:21])[N:11]([CH3:20])[C:12]=2[C:16]([O:18]C)=[O:17])[C:7]1=[O:24].[Li+].[OH-].Cl>C1COCC1.CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[F:28])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:22][CH3:23])[C:10](=[O:21])[N:11]([CH3:20])[C:12]=2[C:16]([OH:18])=[O:17])[C:7]1=[O:24]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 69058384Methyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Product 1

HCID 690633856-(3-Chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate (14.3 g, 35 mmol) in THF (1501 mL) and MeOH (150 mL) was added LiOH (2.74 g, 114 mmol) dissolved in 114 mL water and the reaction was heated to 50° C. for 45 minutes. HPLC showed completion. The reaction was neutralized with 1N HCl and cooled to room temperature. THF was removed in vacuo, and the resulting slurry was partitioned between CHCl3 and 5% aqueous HCl. The aqueous was washed with additional CHCl3. The combined organics were dried over sodium sulfate, filtered, and concentrated to dryness to afford the desired product as a pale yellow foam. The material was crystallized from ethyl acetate to give a light yellow solid.

Workup

  1. temperaturecooled to room temperature
  2. customTHF was removed in vacuo
  3. customthe resulting slurry was partitioned between CHCl3 and 5% aqueous HCl
  4. washThe aqueous was washed with additional CHCl3
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-8180ba4d769c41049f5223035641027a
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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