Sodium hydride → HCID 86718370, compound

HRID 1518762Notes

Reaction equation

HRID 1518762 reaction equation
CS([O:5][CH2:6][C@@H:7]([CH3:23])[C@H:8]([N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:15])[C:9]1[O:10][CH:11]=[CH:12][CH:13]=1)(=O)=O.[H-].[Na+]>C1COCC1>[O:10]1[CH:11]=[CH:12][CH:13]=[C:9]1[C@@H:8]([N:14]([CH3:15])[C:16](=[O:17])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C@H:7]([CH3:23])[CH2:6][O:5][C@H:13]1[CH2:12][CH2:11][O:10][CH2:9]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 86718369HCID 86718369, compound2×

Product 1

HCID 86718370HCID 86718370, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2.16a in THF (6 mL) was added NaH (120 mg, 60% in mineral oil, 3 mmol, 8 equiv.) at 0° C. The mixture was stirred at room temperature for 30 minutes. After cooled down to 0° C. in an ice bath, to the solution was added (2S,3S)-3-((tert-butoxycarbonyl)(methyl)amino)-3-(furan-2-yl)-2-methylpropyl methanesulfonate in THF (2 mL) was added and the resulting mixture was heated to reflux for 16 hours. The reaction was quenched at room temperature by addition of saturated aqueous NH4Cl solution. The mixture was neutralized to pH=7 by addition of 0.5 M KHSO4 aq solution. The aqueous layer was extracted EtOAc. The combined organic layer was washed brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (EtOAc/heptane, 15-50%) to give product 2.16b (50 mg, 39% yield). MS (m/z): 340 [M+1]. 1H NMR (CDCl3, 400 MHz) 7.36 (dd, J=1.96, 0.78 Hz, 1H) 6.32 (dd, J=3.33, 1.76 Hz, 1H) 6.17-6.25 (br. d., 1H) 5.08-5.21 (br. dd, 1H) 3.92 (br. s., 1H) 3.76-3.86 (m, 2H) 3.66-3.76 (m, 2H) 3.27 (br. s., 1H) 3.08 (br. s., 1H) 2.71 (s, 3H) 2.32-2.45 (m, 1H) 1.74-1.91 (m, 2H) 1.58 (s, 1H) 1.41-1.53 (m, 9H) 1.03 (d, J=6.65 Hz, 3H)

Workup

  1. temperatureAfter cooled down to 0° C. in an ice bath, to the solution
  2. additionwas added
  3. temperaturethe resulting mixture was heated
  4. temperatureto reflux for 16 hours
  5. customThe reaction was quenched at room temperature by addition of saturated aqueous NH4Cl solution
  6. additionThe mixture was neutralized to pH=7 by addition of 0.5 M KHSO4 aq solution
  7. extractionThe aqueous layer was extracted EtOAc
  8. washThe combined organic layer was washed brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel column chromatography (EtOAc/heptane, 15-50%)

Sources & evidence

ORD record
ord-3e6678ff44d74d179fa6fa88e2d4655e
Source dataset
uspto-grants-2015_07
Patent number
US09072696B2

Reaction notes

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