Sodium hydride → HCID 178448634, compound

HRID 43292Notes

Reaction equation

HRID 43292 reaction equation
[CH2:1]([OH:5])[C@@H:2]([OH:4])[CH3:3].[H-].[Na+].[CH2:8]([N:12]1[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][C:15]=2[S:14]/[C:13]/1=[N:21]\[C:22](=[O:34])[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1F)[CH2:9][CH2:10][CH3:11]>C1COCC1.C([O-])(O)=O.[Na+]>[CH2:8]([N:12]1[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][C:15]=2[S:14]/[C:13]/1=[N:21]\[C:22](=[O:34])[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:24]=1[O:5][CH2:1][C@@H:2]([OH:4])[CH3:3])[CH2:9][CH2:10][CH3:11]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 439846(S)-propane-1,2-diolHCID 178448621HCID 178448621, compound

Product 1

HCID 178448634HCID 178448634, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-propane-1,2-diol (52 mg, 0.68 mmol) in THF (1 mL) was treated with NaH (60% dispersion; 27 mg, 0.68 mmol) at room temperature for 20 minutes. The mixture was cooled to 0° C. and a solution of Example 18B (90 mg, 0.23 mmol) in THF (1 mL) was added. The mixture was allowed to warm to room temperature, and stirred for 4 hours. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 19 mg (19%) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.48 Hz, 3H) 1.28 (d, J=6.41 Hz, 3H) 1.47-1.59 (m, 2H) 1.88-1.98 (m, 2H) 3.87 (t, J=8.85 Hz, 1H) 4.21-4.31 (m, 1H) 4.35 (dd, J=9.15, 2.75 Hz, 1H) 4.51-4.59 (m, 2H) 7.12 (d, J=8.85 Hz, 1H) 7.72 (dd, J=8.54, 2.14 Hz, 2H) 8.51 (d, J=1.83 Hz, 2H) 8.75 (s, 1H); MS (DCI/NH3) m/z 454 (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-3b298750d62645b080c462352e5bae32
Source dataset
uspto-grants-2013_09
Patent number
US08536336B2

Reaction notes

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