Sodium Carbonate → 2-Methyl-5-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridine

HRID 1051397Notes

Reaction equation

HRID 1051397 reaction equation
[F:1][C:2]([F:26])([F:25])[CH:3]([CH2:8][N:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH2:10]1)[CH2:4][C:5](O)=[O:6].[CH3:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]([NH:34][NH2:35])=O)=[CH:30][N:29]=1.O=P(Cl)(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>>[CH3:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]2[O:6][C:5]([CH2:4][CH:3]([CH2:8][N:9]3[CH2:14][CH2:13][CH2:12][CH:11]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:22])[F:24])[CH:16]=4)[CH2:10]3)[C:2]([F:26])([F:1])[F:25])=[N:35][N:34]=2)=[CH:30][N:29]=1

Participants

5

Reactant 4

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 51510126-Methylpyridine-3-carbohydrazideHCID 901035704,4,4-Trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanoic acid

Product 1

HCID 752022122-Methyl-5-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridineYield 15.3%

Conditions

Temperature
110 °C

Procedure

To a round-bottomed flask (5 ml) was added 4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)-piperidin-1-yl)methyl)butanoic acid (60 mg, 157 μmol), 6-methylnicotinohydrazide (23.7 mg, 157 μmol) and POCl3 (1.64 g, 1 mL, 10.7 mmol). The reaction mixture was heated to reflux at 110° C. for 4 hr. The crude reaction mixture was allowed to cool to room temperature, poured into ice/water and made basic with a saturated solution of Na2CO3. The reaction mixture was extracted with ethyl acetate, washed with brine and H2O, dried over MgSO4, filtered and concentrated. The resultant residue was purified on a silica column (100% hexane to 60% ethyl acetate/hexane gradient) to afford 12 mg (15%) of 2-methyl-5-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethyl-phenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridine as an off-white solid. MH+=499.

Workup

  1. temperatureThe reaction mixture was heated
  2. customThe crude reaction mixture
  3. temperatureto cool to room temperature
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. washwashed with brine and H2O
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resultant residue was purified on a silica column (100% hexane to 60% ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-1f452570dd25479aa9ecdd71792dc480
Source dataset
uspto-grants-2016_07
Patent number
US09388172B2

Reaction notes

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