Neopentyl alcohol → HCID 10047615, compound

HRID 891336Notes

Reaction equation

HRID 891336 reaction equation
[F:1][C:2]([F:23])([F:22])[CH2:3][N:4]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[CH:6]=[N:5]1.[CH2:24]([OH:29])[C:25]([CH3:28])([CH3:27])[CH3:26].[H-].[Na+]>CN(C=O)C>[F:1][C:2]([F:23])([F:22])[CH2:3][N:4]1[C:9](=[O:10])[C:8]([O:29][CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[CH:6]=[N:5]1

Participants

5

Reactant 3

HCID 6404Neopentyl alcoholHCID 24758Sodium hydrideHCID 219343142-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

Product 1

HCID 10047615HCID 10047615, compoundYield 79.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(2,2,2-Trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (150 mg, 0.41 mmol), prepared in Example 193E, and neopentyl alcohol (43 mg, 0.49 mmol) were dissolved in DMF (2 mL) and NaH (25 mg, 0.62 mmol, 60% in mineral oil) was added with shaking and left overnight. The reaction mixture was carefully quenched with saturated NH4Cl solution, diluted with ethyl acetate and extracted with 1 N HCl, twice, then water, 3 times, and then dried over MgSO4. After filtration of the drying agent and concentration of the filtrate in vacuo, the residue was purified by chromatography on silica gel (Biotage 40S) eluted with 2:1 hexanes-ethyl acetate. The product fractions were combined and evaporated to provide the title compound (yield: 137 mg, 76%). mp 145-146° C. 1H NMR (300 MHz, DMSO-d6) δ 0.76 (s, 9H), 3.28 (s, 3H), 4.06 (s, 2H), 5.02 (q, J=9 Hz, 2H), 7.88 (d, J=8 Hz, 2H), 8.04 (d, J=8 Hz, 2H), 8.13 (s, 1H). MS (DCI/NH3) m/z 419 (M+H)+, 436 (M+NH4)+. Anal. calc. for C18H21F3N2O4S: C, 51.67; H, 5.06; N, 6.69. Found: C, 51.47; H, 5.12; N, 6.48.

Workup

  1. customThe reaction mixture was carefully quenched with saturated NH4Cl solution
  2. additiondiluted with ethyl acetate
  3. extractionextracted with 1 N HCl
  4. dry with materialtwice, then water, 3 times, and then dried over MgSO4
  5. filtrationAfter filtration of the drying agent and concentration of the filtrate in vacuo
  6. customthe residue was purified by chromatography on silica gel (Biotage 40S)
  7. washeluted with 2:1 hexanes-ethyl acetate
  8. customevaporated

Sources & evidence

ORD record
ord-0aaf9ae5a0694d4786e6236b063aaedd
Source dataset
uspto-grants-2006_02
Patent number
US07001895B2

Reaction notes

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