Sodium hydride → HCID 131735515, compound

HRID 522208Notes

Reaction equation

HRID 522208 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][CH:15]=[C:16]([I:17])[C:9]=23)[CH:7]=1.[H-].[Na+].[CH3:22][Si:23]([CH3:30])([CH3:29])[CH2:24][CH2:25][O:26][CH2:27]Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[N:14]([CH2:27][O:26][CH2:25][CH2:24][Si:23]([CH3:30])([CH3:29])[CH3:22])[CH:15]=[C:16]([I:17])[C:9]=23)[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 118274330HCID 118274330, compound

Product 1

HCID 131735515HCID 131735515, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

A solution of Example 14B (15.1 g, 41.0 mmol) in tetrahydrofuran under nitrogen was cooled to −8° C. and 60% sodium hydride in mineral oil (2.461 g, 61.5 mmol) was added in portions at a rate such that the temperature was maintained at or below −5° C. The solution was stirred 30 minutes at −5° C. and 2-(trimethylsilyl)ethoxymethyl chloride (8.73 mL, 49.2 mmol) was added dropwise over 15 minutes. The mixture was stirred for 30 minutes at −5° C. and allowed to warm to ambient temperature and stirred overnight. The reaction was quenched carefully with aqueous saturated ammonium chloride and diluted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified on an Analogix MPLC using a silica gel column eluting with 100% heptane followed by 7% ethyl acetate/heptanes to provide the title compound. MS (ESI+) m/z 498.8 (M+H)+.

Workup

  1. temperaturewas maintained at or below −5° C
  2. stirringThe mixture was stirred for 30 minutes at −5° C.
  3. temperatureto warm to ambient temperature
  4. stirringstirred overnight
  5. customThe reaction was quenched carefully with aqueous saturated ammonium chloride
  6. additiondiluted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified on an Analogix MPLC
  12. washeluting with 100% heptane

Sources & evidence

ORD record
ord-57999df62123443cb86f0c1a2662c31e
Source dataset
uspto-grants-2016_05
Patent number
US09328112B2

Reaction notes

Loading…