Sodium hydride → HCID 118117552, compound

HRID 1747211Notes

Reaction equation

HRID 1747211 reaction equation
[H-].[Na+].Cl[CH2:4][C:5]([NH:7][C@@H:8]([CH2:17][OH:18])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([I:16])[CH:11]=1)=[O:6]>C1COCC1>[I:16][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][CH:13]=1)[CH2:9][C@H:8]1[NH:7][C:5](=[O:6])[CH2:4][O:18][CH2:17]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 118117773HCID 118117773, compound

Product 1

HCID 118117552HCID 118117552, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

NaH 60% Dispersion in mineral oil (0.93 g, 23.2 mmol) was added portionwise to a 0° C. solution of 2-chloro-N—[(R)-1-hydroxymethyl-2-(3-iodo-phenyl)-ethyl]-acetamide A-9 (3.72 g, 10.5 mmol) in THF (100 mL) under argon and the resulting suspension was warmed to RT and stirred for 1 h. The reaction mixture was cooled back to 0° C. before being quenched with water and concentrated in vacuo. The remaining aqueous phase was extracted with DCM (3×) and the combined organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo to give the crude product that was purified by flash chromatography (eluting with a gradient of 50% to 100% EtOAc in hexane) to give the title compound as a white solid. LC-MS B: tR=0.72 min; [M+H+MeCN]+=359.01; 1H NMR (CDCl3) δH: 7.64 (d, J=7.9 Hz, 1H), 7.59 (s, 1H), 7.18 (m, 1H), 7.10 (t, J=7.7 Hz, 1H), 6.25 (s, 1H), 4.20 (s, 2H), 3.91 (dd, J1=11.7 Hz, J2=3.7 Hz, 1H), 3.76 (m, 1H), 3.60 (dd, J1=11.7 Hz, J2=6.1 Hz, 1H), 2.87 (dd, J1=13.6 Hz, J2=6.0 Hz, 1H), 2.72 (dd, J1=13.6 Hz, J2=8.5 Hz, 1H).

Workup

  1. custombefore being quenched with water
  2. concentrationconcentrated in vacuo
  3. extractionThe remaining aqueous phase was extracted with DCM (3×)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give the crude product that
  9. customwas purified by flash chromatography (
  10. washeluting with a gradient of 50% to 100% EtOAc in hexane)

Sources & evidence

ORD record
ord-25beb28106c84ae7a55b5a5afdee8687
Source dataset
uspto-grants-2015_10
Patent number
US09150566B2

Reaction notes

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