tert-Butyl bromoacetate → Methyl 2-(2-tert-butoxy-2-oxoethyl)-6-(3-chloro-4-fluorobenzyl)-4-hydroxy-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate

HRID 18003

Reaction equation

HRID 18003 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][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>CO.CS(C)=O.C(OCC)(=O)C>[C:38]([O:37][C:35](=[O:36])[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])([CH3:41])([CH3:40])[CH3:39]

Participants

7

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497, compound

Product 1

HCID 66997817Methyl 2-(2-tert-butoxy-2-oxoethyl)-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 (0.50 g, 1.31 mmol; Example 1, Step 9) and magnesium methoxide in methanol (6.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (13 mL) was heated at 60° C. for one hour. Methanol was exhaustively removed under vacuum over 45 minutes. The resultant DMSO solution was treated with tert-butyl bromoacetate (1.80 g, 10.50 mmol) and stirred at 50° C. under an atmosphere of nitrogen for one hour. The reaction mixture was diluted with ethyl acetate and washed with ice cold dilute hydrochloric acid. The organic extract was washed with aqueous sodium thiosulfate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was triturated with a mixture of diethyl ether and ethyl acetate. The solid precipitated was collected by filtration to provide the title compound. ES MS M+1=495

Workup

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. washwashed with ice cold dilute hydrochloric acid
  3. extractionThe organic extract
  4. washwas washed with aqueous sodium thiosulfate, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was triturated with a mixture of diethyl ether and ethyl acetate
  9. customThe solid precipitated
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-a5504c2c50894d32a7c1fc4dec745e87
Source dataset
uspto-grants-2010_06
Patent number
US07741315B2

Linked notes

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