Sodium Bicarbonate → 3-[2-(Piperidin-4-yloxy)-6-(trifluoromethyl)pyridin-4-yl]oxetan-3-ol

HRID 717896Notes

Reaction equation

HRID 717896 reaction equation
[OH:1][C:2]1([C:6]2[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[N:9]=[C:8]([O:16][CH:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)[CH:7]=2)[CH2:5][O:4][CH2:3]1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.OS(O)(=O)=O>[NH:20]1[CH2:19][CH2:18][CH:17]([O:16][C:8]2[CH:7]=[C:6]([C:2]3([OH:1])[CH2:5][O:4][CH2:3]3)[CH:11]=[C:10]([C:12]([F:13])([F:15])[F:14])[N:9]=2)[CH2:22][CH2:21]1

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 86706874HCID 86706874, compound

Product 1

HCID 867068753-[2-(Piperidin-4-yloxy)-6-(trifluoromethyl)pyridin-4-yl]oxetan-3-ol

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 1118Sulfuric AcidCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 4-{[4-(3-hydroxyoxetan-3-yl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate (0.080 g, 0.17 mmol, from Step 2) in 1,4-dioxane (1.0 mL) was treated with a few drops of water and six drops of concentrated H2SO4 and was stirred overnight. The mixture was made basic with 10 mL of saturated sodium bicarbonate solution and the product was extracted with three portions of DCM. The combined extracts were dried over sodium sulfate, filtered and concentrated to afford crude product, which was used directly in the next step (44 mg, 81%). 1H NMR (300 MHz, CDCl3) δ 7.58 (d, J=1.2 Hz, 1H), 7.18 (s, 1H), 5.22 (tt, J=8.2, 3.9 Hz, 1H), 4.91 (d, J=7.4 Hz, 2H), 4.78 (d, J=7.4 Hz, 2H), 3.10 (dt, J=11.9, 4.3 Hz, 2H), 2.79 (ddd, J=12.5, 9.1, 3.1 Hz, 2H), 2.16-1.98 (m, 2H), 1.70 (dtd, J=12.7, 8.8, 3.8 Hz, 2H). 19F NMR (282 MHz, CDCl3) δ −68.76 (s). LCMS (M+H)+: 319.1.

Workup

  1. extractionthe product was extracted with three portions of DCM
  2. dry with materialThe combined extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford crude product, which

Sources & evidence

ORD record
ord-3128f6aec17b44d1ae789f36564c1f08
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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