Sodium hydride → HCID 67375645, compound

HRID 401973Notes

Reaction equation

HRID 401973 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+].[CH2:17]([C:21]1[N:22]=[N:23][C:24](Cl)=[C:25]([C:40]([F:43])([F:42])[F:41])[C:26]=1[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)=[CH:29][CH:28]=1)[CH2:18][CH2:19][CH3:20]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:24]2[N:23]=[N:22][C:21]([CH2:17][CH2:18][CH2:19][CH3:20])=[C:26]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH:34]4[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]4)=[CH:29][CH:28]=3)[C:25]=2[C:40]([F:43])([F:42])[F:41])[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 86657816HCID 86657816, compound

Product 1

HCID 67375645HCID 67375645, compoundYield 20.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.45 mmol, 0.29 g) in anhydrous DMF (1 mL) at room temperature was added sodium hydride (60% dispersion in mineral oil) (4.36 mmol, 0.175 g) and continued stirring for 10 min. To this was added a solution of 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-5-trifluoromethyl-pyridazine (72.5 mmol, 25.0 g) in anhydrous DMF (1 mL). After 30 minutes, no starting material was remaining as indicated by LCMS. The reaction was quenched with water (20 mL) and extracted with ethyl acetate (2×20 mL). The combined organic layer was washed with brine (10 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on 24 g SiO2 cartridge using an ethyl acetate/hexanes gradient to give 4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-4-trifluoromethyl-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (0.17 g).

Workup

  1. waitAfter 30 minutes
  2. customThe reaction was quenched with water (20 mL)
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washThe combined organic layer was washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on 24 g SiO2 cartridge

Sources & evidence

ORD record
ord-949e7bf18c1c4dbc93caad0ecfec7d15
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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