Sodium hydride → HCID 86706859, compound

HRID 717878Notes

Reaction equation

HRID 717878 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.Cl[C:18]1[CH:19]=[C:20]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[N:30]=1)[C:21]([O:23]C(C)(C)C)=[O:22]>O1CCCC1>[C:13]([O:12][C:10]([N:7]1[CH2:6][CH2:5][CH:4]([O:3][C:18]2[CH:19]=[C:20]([CH:28]=[C:29]([C:31]([F:34])([F:32])[F:33])[N:30]=2)[C:21]([OH:23])=[O:22])[CH2:9][CH2:8]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 86666515HCID 86666515, compound

Product 1

HCID 86706859HCID 86706859, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To sodium hydride (60% in mineral oil, 0.36 g, 8.9 mmol) in tetrahydrofuran (15 mL) at 0° C. was added tert-butyl 4-hydroxypiperidine-1-carboxylate (1.8 g, 8.9 mmol, Aldrich). The reaction mixture was allowed to reach room temperature and stir for 1 hour. A solution of tert-butyl 2-chloro-6-(trifluoromethyl)isonicotinate (1.0 g, 3.6 mmol, from Step 1) in tetrahydrofuran (4.9 mL, 60. mmol) was introduced and the mixture was stirred at room temperature over five nights. The mixture was quenched by the careful addition of 1N NaOH (15 mL) and allowed to stir overnight. The reaction was diluted with additional water and the aqueous layer was washed with Et2O. The aqueous layer was then acidified by the addition of c.HCl to achieve pH˜3. The product was extracted with three portions of ethyl acetate. The combined EtOAc extracts were dried over sodium sulfate, filtered and concentrated. The product was used without further purification. LCMS (M-tBu+H)+: 335.1.

Workup

  1. customto reach room temperature
  2. stirringthe mixture was stirred at room temperature over five nights
  3. customThe mixture was quenched by the careful addition of 1N NaOH (15 mL)
  4. stirringto stir overnight
  5. additionThe reaction was diluted with additional water
  6. washthe aqueous layer was washed with Et2O
  7. additionThe aqueous layer was then acidified by the addition of c
  8. extractionThe product was extracted with three portions of ethyl acetate
  9. dry with materialThe combined EtOAc extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe product was used without further purification

Sources & evidence

ORD record
ord-4ca46adef05d42549b3e60a3d05f6afb
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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