Sodium hydride → HCID 54255406, compound

HRID 362790Notes

Reaction equation

HRID 362790 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][C:11]([C:13]2[CH:18]=[C:17]([O:19][CH3:20])[C:16]([O:21][CH3:22])=[C:15]([O:23][CH3:24])[CH:14]=2)=[O:12])[CH2:4][CH2:3]1.[H-].[Na+].[NH2:27][C:28]1[C:33]2[CH2:34][CH2:35][CH2:36][O:37][C:32]=2[C:31]([C:38](O)=[O:39])=[CH:30][C:29]=1[Cl:41].C(N1C=CN=C1)(N1C=CN=C1)=O>O1CCCC1.C(#N)C>[NH2:27][C:28]1[C:33]2[CH2:34][CH2:35][CH2:36][O:37][C:32]=2[C:31]([C:38]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][CH2:10][C:11](=[O:12])[C:13]3[CH:18]=[C:17]([O:19][CH3:20])[C:16]([O:21][CH3:22])=[C:15]([O:23][CH3:24])[CH:14]=3)[CH2:6][CH2:7]2)=[O:39])=[CH:30][C:29]=1[Cl:41]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 10489495HCID 10489495, compoundHCID 54506059HCID 54506059, compound

Product 1

HCID 54255406HCID 54255406, compoundYield 18.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

4-(4-hydroxy-1-piperidinyl)-1-(3,4,5-trimethoxyphenyl)-1-butanone (3.3 g) was added to a solution of sodium hydride (0.4 g) in tetrahydrofuran (100 ml) (solution I) under a N2 flow. A mixture of 5-amino-6-chloro-3,4-dihydro-2H-1-benzopyran-8-carboxylic acid (2.14 g) and 1,1'-carbonylbis-1H-imidazole (2 g) in acetonitril (100 ml) was stirred for 2 hours at room temperature and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (100 ml) (solution II). At room temperature, solution (II) was poured out into solution (I) and the reaction mixture was stirred for 4 hours at room temperature. The solvent was evaporated. The residue was diluted with water and extracted twice with CH2Cl2. The separated organic layer was washed with water, dried over MgSO4, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /hexane/(CH3OH/NH3) 50/42/3). The desired fractions were collected and the solvent was evaporated. The residue (2.3 g) was purified by high-performance liquid chromatography over silica gel (eluent: CH2Cl2 /CH3OH 90/10). The pure fractions were collected and the solvent was evaporated. The residue (1.2 g) was crystallized from diisopropyl ether. The precipitate was filtered off and dried, yielding 0.93 g of 1-[4-oxo-4-(3,4,5-trimethoxyphenyl)butyl]-4-piperidinyl 5-amino-6-chloro-3,4-dihydro-2H-benzopyran-8-carboxylate (17%); mp. 112.7° C. (compound 8).

Workup

  1. customthe solvent was evaporated
  2. dissolutionThe residue was dissolved in tetrahydrofuran (100 ml) (solution II)
  3. additionAt room temperature, solution (II) was poured out into solution (I)
  4. stirringthe reaction mixture was stirred for 4 hours at room temperature
  5. customThe solvent was evaporated
  6. additionThe residue was diluted with water
  7. extractionextracted twice with CH2Cl2
  8. washThe separated organic layer was washed with water
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customthe solvent was evaporated
  12. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /hexane/(CH3OH/NH3) 50/42/3)
  13. customThe desired fractions were collected
  14. customthe solvent was evaporated
  15. customThe residue (2.3 g) was purified by high-performance liquid chromatography over silica gel (eluent: CH2Cl2 /CH3OH 90/10)
  16. customThe pure fractions were collected
  17. customthe solvent was evaporated
  18. customThe residue (1.2 g) was crystallized from diisopropyl ether
  19. filtrationThe precipitate was filtered off
  20. customdried

Sources & evidence

ORD record
ord-16b23937e41342399483e229ff6707b9
Source dataset
uspto-grants-1999_02
Patent number
US05872131

Reaction notes

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