Sodium Bicarbonate → HCID 58774430, compound

HRID 1785397Notes

Reaction equation

HRID 1785397 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.CO[N:25]=[C:26]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[CH2:27]Br.CC(C)([O-])C.[K+].C([O-])(O)=O.[Na+]>CC(C)=O>[F:35][C:32]1[CH:33]=[CH:34][C:29]([C:26]2[N:25]=[C:2]3[CH:3]=[C:4]([CH:7]4[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=5)=[O:14])[CH2:9][CH2:8]4)[CH:5]=[CH:6][N:1]3[CH:27]=2)=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 69053202Benzyl 4-pyridin-4-ylpiperidine-1-carboxylateHCID 725643092-Bromo-1-(4-fluorophenyl)ethanone O-methyloxime

Product 1

HCID 58774430HCID 58774430, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A 500 mL round bottom flask was charged with crude pyridine 33 (8.20 g, 27.7 mmol), acetone (300 mL), and O-methyloxime 30 (6.8 g, 27.7 mmol), and the reaction mixture was allowed to stir at room temperature for 12 hours, after which thin-layer chromatography testing suggested that pyridinyl salt formation was complete. The reaction was then concentrated under reduced pressure in a 500 mL round bottom flask, and charged with methanol (200 mL), additional pyridinyl salt prepared previously (600 mg), and potassium tert-butoxide (3.90 g, 34.6 mmol). The resulting mixture was heated to 65° C. for 4 hours. The reaction mixture was then poured into 400 mL of an aqueous solution saturated with NaHCO3 and extracted with 3×250 mL of methylene chloride. The organic fractions were pooled, dried over Na2SO4, filtered, concentrated under reduced pressure, then dissolved in a minimum volume of CH2Cl2, then loaded onto 3×40 g Isco RediSep normal phase silica cartridges, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% methylene chloride and ended at 90% methylene chloride, 9% methanol, and 1% concentrated ammonium hydroxide. Fractions containing the desired product were pooled and concentrated under reduced pressure; fractions containing impure product were pooled, concentrated under reduced pressure, then dissolved in a minimum volume of CH2Cl2, and loaded onto 2×40 g Isco RediSep normal phase silica cartridges, and purified on an Isco OptiX10 CombiFlash instrument using a gradient which started at 100% heptane and ended at 100% ethyl acetate. This process was repeated once on the remaining impure product. Yield of 34: 3.10 g (26%). 1H NMR (500 MHz, CDCl3) δ 1.50 (m, 2H), 1.76 (m, 2H), 2.55 (m, 1H), 2.77 (bs, 2H), 4.45 (bs, 2H), 5.04 (s, 2H), 6.48 (d, J=5.3 Hz, 1H), 6.96 (t, J=8.8 Hz, 2H), 7.24 (m, 6H), 7.57 (s, 1H), 7.76 (m, 2H), 7.86 (d, J=7.1 Hz, 1H). MS (ESI+) 430.2.

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure in a 500 mL round bottom flask
  2. additioncharged with methanol (200 mL), additional pyridinyl salt
  3. temperatureThe resulting mixture was heated to 65° C. for 4 hours
  4. extractionextracted with 3×250 mL of methylene chloride
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutiondissolved in a minimum volume of CH2Cl2
  9. custompurified on an Isco OptiX10 CombiFlash instrument
  10. additionFractions containing the desired product
  11. concentrationconcentrated under reduced pressure
  12. additionfractions containing impure product
  13. concentrationconcentrated under reduced pressure
  14. dissolutiondissolved in a minimum volume of CH2Cl2
  15. custompurified on an Isco OptiX10 CombiFlash instrument

Sources & evidence

ORD record
ord-6ca4f6d6afc34f95b1150242e1d90c51
Source dataset
uspto-grants-2009_03
Patent number
US07504501B2

Reaction notes

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