Potassium Carbonate → HCID 69269462, compound

HRID 751532Notes

Reaction equation

HRID 751532 reaction equation
CO[C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][CH2:11]C(OC)OC)[C:5]=1[N+:17]([O-])=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][C:37](=O)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].C([BH3-])#N.[Na+].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[Pd].O>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37]([N:17]2[C:5]3[C:6](=[CH:7][CH:8]=[CH:9][C:4]=3[CH2:3][OH:20])[CH:10]=[CH:11]2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 21226445Aluminium lithium hydrideHCID 69268597HCID 69268597, compound

Product 1

HCID 69269462HCID 69269462, compoundYield 42.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Hydrogenate 3-(3,3-dimethoxypropyl)-2-nitrobenzoic acid methyl ester (7.8 g, 0.029 mol) in 100 mL of tetrahydrofuran with 0.743 g 5% Pd/C at 60 psi for 24 hours. Filter and concentrate. Dissolve the resulting product in 30 mL of tetrahydrofuran, and add it dropwise to a suspension of lithium aluminum hydride (2.2 g, 0.058 mol) in 100 mL of tetrahydrofuran at 0° C. Allow the reaction to warm to room temperature, and stir for 2 hours. Quench the mixture with saturated Rochelle salt and extract with ethyl acetate. Dry and concentrate. Dissolve the product in in 30 mL of acetic acid and add 4-oxopiperidine-1-carboxylic acid tert-butyl ester (6.3 g, 0.032 mol). After 10 minutes, add sodium cyanoborohydride (9.2 g, 0.032 mol) and stir the mixture for 1 hour. Heat the mixture at 100° C. for 3 hours, cool, and pour into water. Neutralize the solution with potassium carbonate and extract with ethyl acetate. Dry and concentrate. Dissolve the crude mixture in 100 mL of methanol and treat with 20 mL of 1N sodium hydroxide for 3 hours. Remove the methanol in vacuo, and extract the mixture with ethyl acetate. Dry and concentrate. Purify by flash chromatography using 4:1 hexanes/ethyl acetate to give 4.1 g of 4-(7-hydroxymethylindol-1-yl)piperidine-1-carboxylic acid tert-butyl ester. FAB MS 330.

Workup

  1. filtrationFilter
  2. concentrationconcentrate
  3. dissolutionDissolve the resulting product in 30 mL of tetrahydrofuran
  4. additionadd it
  5. customthe reaction
  6. customQuench the mixture with saturated Rochelle salt
  7. extractionextract with ethyl acetate
  8. customDry
  9. concentrationconcentrate
  10. dissolutionDissolve the product in in 30 mL of acetic acid
  11. waitAfter 10 minutes
  12. stirringstir the mixture for 1 hour
  13. temperatureHeat the mixture at 100° C. for 3 hours
  14. temperaturecool
  15. extractionextract with ethyl acetate
  16. customDry
  17. concentrationconcentrate
  18. dissolutionDissolve the crude mixture in 100 mL of methanol
  19. additiontreat with 20 mL of 1N sodium hydroxide for 3 hours
  20. customRemove the methanol in vacuo
  21. extractionextract the mixture with ethyl acetate
  22. customDry
  23. concentrationconcentrate
  24. customPurify by flash chromatography

Sources & evidence

ORD record
ord-e0b654b5fea04fdfb90507bd18c5a608
Source dataset
uspto-grants-2008_07
Patent number
US07405305B2

Reaction notes

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