Sodium Sulfate → HCID 86738230, compound

HRID 851057Notes

Reaction equation

HRID 851057 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:7]1([C:10]([N:12]2[CH2:17][CH2:16][C@H:15]([O:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C@H:14]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:13]2)=O)[CH2:9][CH2:8]1.S([O-])([O-])(=O)=O.[Na+].[Na+].[CH:39](/[C:44]([OH:46])=[O:45])=[CH:40]\[C:41]([OH:43])=[O:42]>O1CCCC1.CCOCC.C(O)C.CO.CC(C)=O>[C:44]([OH:46])(=[O:45])/[CH:39]=[CH:40]/[C:41]([OH:43])=[O:42].[CH:7]1([CH2:10][N:12]2[CH2:17][CH2:16][C@H:15]([O:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[C@H:14]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:13]2)[CH2:8][CH2:9]1

Participants

9

Reactant 4

HCID 24436Sodium SulfateHCID 444972Fumaric Acid2×HCID 13039272HCID 13039272, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 86738230HCID 86738230, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 3283Diethyl EtherSolvent5×HCID 8028TetrahydrofuranSolvent2×HCID 21894497Aceton-methanolSolvent

Procedure

To a suspension of 0.66 g of lithium aluminum hydride in 50 ml of anhydrous tetrahydrofuran is added, dropwise at room temperature under nitrogen, a solution of 2.93 g of cis-1-cyclopropylcarbonyl-4-(4-fluorophenoxy)-3-phenylpiperidine in 50 ml of tetrahydrofuran. After the addition is complete the mixture is refluxed for 30 minutes, cooled, diluted with 50 ml of ether and cautiously treated with saturated sodium sulfate solution at 0°-10° C. until a flocculent white precipitate is obtained. The solid is filtered, washed with ether and the filtrate concentrated in vacuo. The residue is dissolved in ether (150 ml), washed with saturated sodium chloride solution (75 ml), dried overnight over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a colorless gum. The gum is dissolved in ether (80 ml) and treated dropwise with a solution of 1.04 g of tumaric acid in a mixture of ethanol (15 ml) and ether (60 ml). After stirring for a few hours the colorless solid is filtered, washed with ether and dried to afford a salt. A second crop of solid is obtained from the filtrate. The solids are combined and recrystallized from 25 ml of boiling isopropanol to afford a crystalline solid. The solid and mother liquor are combined and the free base is regenerated. The nearly colorless gum is dissolved in 25% methanol/acetone solution and passed through a small silica gel column. The material thus obtained is dissolved in ether (50 ml) and treated dropwise with a solution of 0.91 g of fumaric acid in a mixture of ethanol (15 ml) and ether (60 ml). After stirring the mixture overnight, the solid is filtered, washed with ether and dried to yield product as a colorless solid, mp 167°-168.5° C.

Workup

  1. additionis added, dropwise at room temperature under nitrogen
  2. additionAfter the addition
  3. temperatureis refluxed for 30 minutes
  4. temperaturecooled
  5. customis obtained
  6. filtrationThe solid is filtered
  7. washwashed with ether
  8. concentrationthe filtrate concentrated in vacuo
  9. dissolutionThe residue is dissolved in ether (150 ml)
  10. washwashed with saturated sodium chloride solution (75 ml)
  11. dry with materialdried overnight over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto afford a colorless gum
  15. filtrationis filtered
  16. washwashed with ether
  17. customdried
  18. customto afford a salt
  19. customA second crop of solid is obtained from the filtrate
  20. customrecrystallized from 25 ml of boiling isopropanol
  21. customto afford a crystalline solid
  22. customThe material thus obtained
  23. stirringAfter stirring the mixture overnight
  24. filtrationthe solid is filtered
  25. washwashed with ether
  26. customdried
  27. customto yield product as a colorless solid, mp 167°-168.5° C.

Sources & evidence

ORD record
ord-c820970c911d48a190347b659cc71ece
Source dataset
uspto-grants-1983_05
Patent number
US04382141

Reaction notes

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