2-Butyn-1-ol → US10023592, Example 388

HRID 518546Notes

Reaction equation

HRID 518546 reaction equation
[CH2:1]([OH:5])[C:2]#[C:3][CH3:4].[H-].[Na+].F[C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][C:10]=1[C:19]1[CH:20]=[C:21]([CH3:27])[C:22](=[O:26])[N:23]([CH3:25])[CH:24]=1>CN(C=O)C>[CH2:1]([O:5][C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][C:10]=1[C:19]1[CH:20]=[C:21]([CH3:27])[C:22](=[O:26])[N:23]([CH3:25])[CH:24]=1)[C:2]#[C:3][CH3:4]

Participants

5

Reactant 3

HCID 129912-Butyn-1-olHCID 24758Sodium hydrideHCID 1180225965-(2-Fluoro-5-methylsulfonylphenyl)-1,3-dimethylpyridin-2-one

Product 1

HCID 118021635US10023592, Example 388Yield 23.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of but-2-yn-1-ol (191 mg, 2.72 mmol) in anhydrous DMF (3 mL) was added NaH (109 mg, 2.72 mmol, 60% in mineral oil) at 0° C. The mixture was stirred at this temperature for 1 hr. The title compound from Step 1 (200 mg, 0.68 mmol) was added and the reaction mixture was stirred at 0° C. for 2 hrs. After this time, it was quenched with sat. NH4Cl solution (20 mL) and extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine (40 mL), dried over Na2SO4, filtered and concentrated to give a crude product that was purified by prep-HPLC to give the title compound (56.01 mg, 23.9%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.88 (dd, J1=8.8 Hz, J2=2.0 Hz, 1H), 7.81 (d, J=2.0 Hz, 1H), 7.46 (s, 2H), 7.24 (d, J=8.8 Hz, 1H), 4.79 (d, J=2.0 Hz, 2H), 3.62 (s, 3H), 3.08 (s, 3H), 2.22 (s, 3H), 1.87 (s, 3H). LCMS: 346.0 (M+H)+

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 2 hrs
  2. customAfter this time, it was quenched with sat. NH4Cl solution (20 mL)
  3. extractionextracted with EtOAc (20 mL×3)
  4. washThe combined organic layers were washed with brine (40 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude product that
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-ac1c49c7523242df863dcbd1adb88b78
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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