HCID 14547436, compound → HCID 22165626, compound

HRID 1032368Notes

Reaction equation

HRID 1032368 reaction equation
C([Li])CCC.CC(C)=O.[C:10](=[O:12])=[O:11].[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[CH:21]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([CH3:31])[NH:24][C:23]([CH2:32][O:33][CH2:34][C:35]#[CH:36])=[C:22]1[C:37]([O:39][CH2:40][CH3:41])=[O:38]>CCCCCC.O1CCCC1>[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[CH:21]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([CH3:31])[NH:24][C:23]([CH2:32][O:33][CH2:34][C:35]#[C:36][C:10]([OH:12])=[O:11])=[C:22]1[C:37]([O:39][CH2:40][CH3:41])=[O:38]

Participants

6

Reactant 3

HCID 14547436HCID 14547436, compoundHCID 18522661Acetone cardiceHCID 178418339Butyllithium

Product 1

HCID 22165626HCID 22165626, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A 1.6M solution of n-butyllithium in hexane (36 ml) was added dropwise over 40 minutes to a stirred, cooled (acetone/cardice bath) solution of 1-{[4-(2,3-dichlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyrid-2-yl]methoxy}prop-2-yne (11.0 g) in tetrahydrofuran (110 ml) and the mixture allowed to warm to -40° over one hour. The mixture was then cooled to -60° and carbon dioxide bubbled through the stirred solution at that temperature for one hour. Carbon dioxide was then bubbled through the mixture for a further one hour whilst it was allowed to warm up to 0°. The mixture was then diluted with water (100 ml) and the layers separated. The aqueous layer was washed with diethyl ether, acidified to pH 1.0 with concentrated hydrochloric acid and extracted into dichloromethane. The combined dichloromethane extracts were dried over MgSO4 and evaporated and the residue triturated with methanol. The resulting solid was collected, washed with methanol and dried to give the title compound (8.87 g) as a hemihydrate containing half a mole of methanol of crystallisation, m.p. 100°.

Workup

  1. temperatureto warm to -40° over one hour
  2. temperatureThe mixture was then cooled to -60°
  3. customcarbon dioxide bubbled through the stirred solution at that temperature for one hour
  4. customCarbon dioxide was then bubbled through the mixture for a further one hour whilst it
  5. temperatureto warm up to 0°
  6. additionThe mixture was then diluted with water (100 ml)
  7. customthe layers separated
  8. washThe aqueous layer was washed with diethyl ether
  9. extractionextracted into dichloromethane
  10. dry with materialThe combined dichloromethane extracts were dried over MgSO4
  11. customevaporated
  12. customthe residue triturated with methanol
  13. customThe resulting solid was collected
  14. washwashed with methanol
  15. customdried

Sources & evidence

ORD record
ord-860953f5da564578b1ec8cbcc50ab207
Source dataset
uspto-grants-1990_09
Patent number
US04957930

Reaction notes

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