Sodium hydride → Ethyl 1-((tert-Butoxycarbonyl)(methyl)amino)-8-fluoro-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1168533Notes

Reaction equation

HRID 1168533 reaction equation
[H-].[Na+].F[C:4]1[C:28]([F:29])=[CH:27][C:26]([I:30])=[CH:25][C:5]=1[C:6]([C:8]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9][NH:10][N:11]([CH3:19])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7]>CN(C)C=O.[Cl-].[Na+].O>[C:15]([O:14][C:12]([N:11]([CH3:19])[N:10]1[C:4]2[C:5](=[CH:25][C:26]([I:30])=[CH:27][C:28]=2[F:29])[C:6](=[O:7])[C:8]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 178472139ethyl 2-(2,3-difluoro-5-iodobenzoyl)-3-[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]prop-2-enoate

Product 1

HCID 12083058Ethyl 1-((tert-Butoxycarbonyl)(methyl)amino)-8-fluoro-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Sodium hydride (0.256 g, 60% oil dispersion) is added to a solution of tert-butyl 2-(2-(2,3-difluoro-5-iodobenzoyl)-3-ethoxy-3-oxoprop-1-enyl)-1-methylhydrazinecarboxylate (Preparation 33, 3.20 g) in N,N-dimethylformamide (18 mL) at room temperature, and the mixture is stirred for 2 h. The reaction mixture is poured into a mixture of 100 mL of ice water and 100 mL of saturated brine. The mixture is extracted 3 times with ethyl acetate. The combined organic layers are dried (Na2SO4) and concentrated under a nitrogen stream overnight. The crude product is purified by chromatography, using 200 g of silica gel packed and eluted with acetone/CH2Cl2/heptane (1/3/6), provided 2.76 g (90%) of the title compound as a white foam. Physical characteristics: 1H NMR (CDCl3) δ8.50, 8.31, 7.67, 4.32, 3.37, 1.49, 1.34, 1.25; 13C NMR (CDCl3) δ168.87, 163.97, 160.01, 155.50, 141.76, 131.84, 131.37, 128.46, 127.24, 110.98, 86.73, 78.64, 61.47, 36.09, 28.00, 14.64; MS (ESI+) m/z 491 (M+H)+; TLC (silica gel GF): Rf=0.44 acetone/CH2Cl2/hexane (1/1/3).

Workup

  1. extractionThe mixture is extracted 3 times with ethyl acetate
  2. dry with materialThe combined organic layers are dried (Na2SO4)
  3. concentrationconcentrated under a nitrogen
  4. waitstream overnight
  5. customThe crude product is purified by chromatography
  6. washeluted with acetone/CH2Cl2/heptane (1/3/6)

Sources & evidence

ORD record
ord-421d9264645145398f57a833574abd2a
Source dataset
uspto-grants-2003_09
Patent number
US06624159B2

Reaction notes

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