Sodium hydride → HCID 67373305, compound

HRID 401990Notes

Reaction equation

HRID 401990 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:18]1[N:23]=[N:22][C:21]([CH:24]2[CH2:27][CH2:26][CH2:25]2)=[C:20]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)=[CH:30][CH:29]=2)[CH:19]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[N:23]=[N:22][C:21]([CH:24]3[CH2:25][CH2:26][CH2:27]3)=[C:20]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH:35]4[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]4)=[CH:32][CH:33]=3)[CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 86657819HCID 86657819, compound

Product 1

HCID 67373305HCID 67373305, compoundYield 80.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.66 mmol, 0.13 g) in anhydrous THF (0.5 mL) at room temperature was added sodium hydride (60% dispersion in mineral oil) (0.88 mmol, 0.035 g) and continued stirring for 10 min. The reaction mixture was cooled to 0° C. using an ice bath. To this was added a solution of 6-chloro-3-cyclobutyl-4-(4-cyclohexyloxy-phenyl)-pyridazine (0.44 mmol, 0.15 g) in THF (0.5 mL). After completion of addition, the reaction mixture was warmed to 65° C. and stirred for 1 hour. After cooling the reaction to room temperature, the reaction was quenched with water (1 mL) and extracted with ethyl acetate (1×3 mL). The ethyl acetate layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a 4 g SiO2 cartridge eluting with a 10-30% ethyl acetate/hexanes gradient to give 4-[6-cyclobutyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (0.18 g).

Workup

  1. additionAfter completion of addition
  2. temperaturethe reaction mixture was warmed to 65° C.
  3. stirringstirred for 1 hour
  4. temperatureAfter cooling
  5. customthe reaction to room temperature
  6. customthe reaction was quenched with water (1 mL)
  7. extractionextracted with ethyl acetate (1×3 mL)
  8. dry with materialThe ethyl acetate layer was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified on a 4 g SiO2 cartridge
  12. washeluting with a 10-30% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-dd410d63a58949fe9822032e44846689
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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