Water → HCID 86657787, compound

HRID 401922Notes

Reaction equation

HRID 401922 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][OH:15])[C@H:10]([O:16][CH2:17][O:18][CH3:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:22]([C:26]1[N:27]=[N:28][C:29](Cl)=[CH:30][C:31]=1[C:32]1[CH:37]=[CH:36][C:35]([O:38][CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:34][CH:33]=1)[CH2:23][CH2:24][CH3:25].O>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:15][C:29]2[N:28]=[N:27][C:26]([CH2:22][CH2:23][CH2:24][CH3:25])=[C:31]([C:32]3[CH:33]=[CH:34][C:35]([O:38][CH:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]4)=[CH:36][CH:37]=3)[CH:30]=2)[C@H:10]([O:16][CH2:17][O:18][CH3:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 866577793-Butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazineHCID 86657786HCID 86657786, compound

Product 1

HCID 86657787HCID 86657787, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (±)-cis-4-hydroxymethyl-3-methoxymethoxy-piperidine-1-carboxylic acid tert-butyl ester (4.64 mmol, 1.28 g) in DMF (5 mL) at room temperature was added sodium hydride (60% dispersion in mineral oil) (13.9 mmol, 0.56 g) and continued stirring for 15 min. The reaction mixture was cooled to 0° C. using an ice bath. To this was added a solution of 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine (Example 14, 2.32 mmol, 0.80 g) in DMF (5 mL). After completion of addition, the reaction mixture was warmed to 50° C. for 2 hours. After cooling to room temperature, the reaction was poured into a mixture of water (100 mL) and ethyl acetate (100 mL). The mixture was shaken and separated. The ethyl acetate layer was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a 40 g SiO2 cartridge using a gradient of ethyl acetate/hexanes to provide (±)-cis-4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-3-methoxymethoxy-piperidine-1-carboxylic acid tert-butyl ester (0.60 g, 44° A). LCMS: m/z 583.9 [M+1].

Workup

  1. additionAfter completion of addition
  2. temperaturethe reaction mixture was warmed to 50° C. for 2 hours
  3. temperatureAfter cooling to room temperature
  4. stirringThe mixture was shaken
  5. customseparated
  6. washThe ethyl acetate layer was washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on a 40 g SiO2 cartridge

Sources & evidence

ORD record
ord-7b49d269ccf6415ebd74ac87ca526e93
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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