Sodium Hydroxide → HCID 86731571, compound

HRID 1430587Notes

Reaction equation

HRID 1430587 reaction equation
Cl.[C:2]([CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][NH:5]1)#[CH:3].[OH-].[Na+].[CH3:12][C:13]1[CH:14]=[CH:15][C:16]([N:22]2[N:26]=[CH:25][CH:24]=[N:23]2)=[C:17]([CH:21]=1)[C:18](Cl)=[O:19]>C1(C)C=CC=CC=1.CCOC(C)=O>[C:2]([CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][N:5]1[C:18]([C:17]1[CH:21]=[C:13]([CH3:12])[CH:14]=[CH:15][C:16]=1[N:22]1[N:26]=[CH:25][CH:24]=[N:23]1)=[O:19])#[CH:3]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 58468226HCID 58468226, compoundHCID 713076952-Ethynylpiperidine hydrochloride

Product 1

HCID 86731571HCID 86731571, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a rapidly-stirred mixture of 2-ethynylpiperidine hydrochloride (329 mg, 2.26 mmol), toluene (5 mL), and 1N NaOH (4.7 mL), cooled at 0° C., was added a solution of 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl chloride (500 mg, 2.26 mmol) in toluene (8 mL) dropwise over 20 mins. The mixture was stirred at 0° C. for 20 mins, then allowed to warm to ambient temperature. After 1 h, the solution was diluted with EtOAc and the layers separated. Brine was added to the aqueous layer and it was extracted with EtOAc. The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel flash chromatography eluting with 0-60% EtOAc in hexanes to provide (2-ethynylpiperidin-1-yl)[5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone as a collapsing white foam. The compound gave a high resolution mass spectrum (ES+) m/z of 259.1553, calculated for M+H+ [C17H18N4O: 295.1553]. 1H NMR δ (ppm) (CDCl3): 7.75-7.86 (3H, m), 7.30-7.34 (1 H, m), 7.18-7.20 (1H, m), 5.76 (1H, d, J=33.6 Hz), 4.50-4.67 (1H, m), 3.20-3.31 (1H, m), 2.91-3.08 (1H, m), 2.43 (3H, s), 2.04-2.36 (1H, m), 1.64-1.91 (2H, m), 1.42-1.61 (1H, m), 1.30-1.37 (1H, m).

Workup

  1. temperatureto warm to ambient temperature
  2. waitAfter 1 h
  3. customthe layers separated
  4. additionBrine was added to the aqueous layer and it
  5. extractionwas extracted with EtOAc
  6. dry with materialThe combined organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by silica gel flash chromatography
  10. washeluting with 0-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-f7c49c108c7744439fe3a9d0cf53d301
Source dataset
uspto-grants-2015_01
Patent number
US08940898B2

Reaction notes

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