1-Bromo-4-chlorobutane → Methyl 2-(4-chlorobutyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

HRID 2066574Notes

Reaction equation

HRID 2066574 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].[CH3:28][O-:29].[Mg+2].C[O-].Br[CH2:34][CH2:35][CH2:36][CH2:37][Cl:38]>CO.CS(C)=O.C(OCC)(=O)C>[Cl:38][CH2:37][CH2:36][CH2:35][CH2:34][N:11]1[C:10](=[O:21])[C:9]([OH:22])=[C:8]2[C:13]([CH2:14][CH2:15][N:6]([CH2:5][C:4]3[CH:24]=[CH:25][C:26]([F:27])=[C:2]([Cl:1])[CH:3]=3)[C:7]2=[O:23])=[C:12]1[C:16]([O:29][CH3:28])=[O:17]

Participants

7

Reactant 3

HCID 813641-Bromo-4-chlorobutaneHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497, compound

Product 1

HCID 66997340Methyl 2-(4-chlorobutyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.80 g, 2.19 mmol) and magnesium methoxide in methanol (10.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (22 mL) was heated at 60° C. for one hour. Methanol was exhaustively removed under vacuum over 45 minutes. The resulting DMSO solution was treated with 1-bromo-4-chlorobutane (1.80 g, 10.50 mmol) and stirred at 60° C. under an atmosphere of nitrogen for one hour. The reaction mixture was diluted with ethyl acetate and washed with dilute hydrochloric acid. The organic extract was washed with 10% aqueous potassium carbonate, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether. The solid precipitated was collected by filtration to provide the title compound. ES MS M+1=471

Workup

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. washwashed with dilute hydrochloric acid
  3. extractionThe organic extract
  4. washwas washed with 10% aqueous potassium carbonate
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was triturated with diethyl ether
  9. customThe solid precipitated
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-225f973bf3234816baf840e6fbb6e549
Source dataset
uspto-grants-2012_10
Patent number
US08293731B2

Reaction notes

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