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Water → 1-cyclopropyl-8-(diphenylmethoxycarbonylmethyl)-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester

HRID 1899
Notes
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Reaction equation

HRID 1899 reaction equation
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])C)(=[O:12])[CH2:4][C:5](OC(C)(C)C)=O.[CH2:18]([O:20][C:21]([C:23]1[C:32](=[O:33])[N:31]2[C:26]([C:27](C)=[C:28](Cl)[C:29]([F:34])=[CH:30]2)=[C:25]([CH:37]2[CH2:39][CH2:38]2)[CH:24]=1)=[O:22])[CH3:19].O>CN(C=O)C>[CH2:18]([O:20][C:21]([C:23]1[C:32](=[O:33])[N:31]2[C:26]([C:27]([CH3:28])=[C:5]([CH2:4][C:3]([O:13][CH:14]([C:16]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]3[CH:37]=[CH:25][CH:24]=[CH:23][CH:21]=3)=[O:12])[C:29]([F:34])=[CH:30]2)=[C:25]([CH:37]2[CH2:39][CH2:38]2)[CH:24]=1)=[O:22])[CH3:19]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 9927245Ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

Product 1

HCID 570602831-cyclopropyl-8-(diphenylmethoxycarbonylmethyl)-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents

1
HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH in DMF with ice bath cooling is added di-t-butyl malonate. After the addition, 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester from Example 253i above is added. The reaction is then heated to 50° to 60° C., and the mixture is poured into water and acidified. The product is extracted into methylene chloride and dried over MgSO4. The residue, after removal of the solvent, is dissolved in methylene chloride and trifluoroacetic acid at room temperature. The solvent is removed under vacuum, and the product is treated with diphenyldiazomethane in methylene chloride and methanol. When the reaction is finished, the solvents are removed under vacuum, and the product is purified by column chromatography to give the title compound.

Workup

  1. temperaturecooling
  2. additionabove is added
  3. temperatureThe reaction is then heated to 50° to 60° C.
  4. extractionThe product is extracted into methylene chloride
  5. dry with materialdried over MgSO4
  6. customThe residue, after removal of the solvent
  7. dissolutionis dissolved in methylene chloride
  8. customat room temperature
  9. customThe solvent is removed under vacuum
  10. additionthe product is treated with diphenyldiazomethane in methylene chloride and methanol
  11. customthe solvents are removed under vacuum
  12. customthe product is purified by column chromatography

Sources & evidence

ORD record
ord-bb91f751bb204267a4e371b6462d78b9
Source dataset
uspto-grants-1998_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05726182

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes