Sodium hydride → HCID 67375294, compound

HRID 401937Notes

Reaction equation

HRID 401937 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:15])([F:14])[CH:10]([CH2:16][OH:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:20]([C:24]1[N:25]=[N:26][C:27](Cl)=[CH:28][C:29]=1[C:30]1[CH:35]=[CH:34][C:33]([O:36][CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:32][CH:31]=1)[CH2:21][CH2:22][CH3:23]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:14])([F:15])[CH:10]([CH2:16][O:17][C:27]2[N:26]=[N:25][C:24]([CH2:20][CH2:21][CH2:22][CH3:23])=[C:29]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH:37]4[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]4)=[CH:34][CH:35]=3)[CH:28]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67373330tert-butyl 4,4-difluoro-3-(hydroxyMethyl)piperidine-1-carboxylateHCID 866577793-Butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine

Product 1

HCID 67375294HCID 67375294, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,4-difluoro-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (0.8 mmol, 0.2 g) in 5 mL of THF was added 60% NaH (4.0 mmol, 96 mg). The mixture was stirred at room temperature for 10 min, then a solution of 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine (Example 14, 0.4 mmol, 0.14 g) was added. The mixture was refluxed for 1 h, quenched with water, extracted with EtOAc. The organic layer was washed with saturated sodium bicarbonate, brine, dried, evaporated, the resulting residue was chromatographed with 20:1 DCM/MeOH to afford 3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-4,4-difluoro-piperidine-1-carboxylic acid tert-butyl ester (150 mg).

Workup

  1. temperatureThe mixture was refluxed for 1 h
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with saturated sodium bicarbonate, brine
  5. customdried
  6. customevaporated
  7. customthe resulting residue was chromatographed with 20:1 DCM/MeOH

Sources & evidence

ORD record
ord-5205098f34ac4f14a00249e71e92b6a8
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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