Sodium hydride → HCID 57771773, compound

HRID 1174953Notes

Reaction equation

HRID 1174953 reaction equation
C[N:2]1CCCC(O)C1.C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[CH3:23][NH:24][C:25]1[O:26][C:27]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][C:28]=2[N:29]=1.[H-].[Na+].[CH3:39][N:40]1[CH2:45][CH2:44][CH2:43][CH:42](OS(C)(=O)=O)[CH2:41]1>C(Cl)Cl.CN(C=O)C.O.C(OCC)(=O)C>[NH3:2].[CH3:23][N:24]([CH:42]1[CH2:43][CH2:44][CH2:45][N:40]([CH3:39])[CH2:41]1)[C:25]1[O:26][C:27]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][C:28]=2[N:29]=1

Participants

12

Reactant 6

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 980163-Piperidinol, 1-methyl-HCID 55266256HCID 55266256, compoundHCID 57771771HCID 57771771, compound

Product 2

HCID 222AmmoniaYield 10%HCID 57771773HCID 57771773, compoundYield 49%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Place 1-methyl-piperidin-3-ol in DCM (10 mL). Add diisopropylethylamine (DIEA) (1.84 mL, 11.15 mmol) followed by methanesulfonyl chloride (0.866 mL, 11.15 mmol). Stir at rt for 17 h. Add DCM (10 mL) and wash the organic layer with 1N NaOH (20 mL). Collect the organic layer, dry over MgSO4, filter, and concentrate in vacuo. Place methyl-(5-nitro-benzooxazol-2-yl)-amine (600 m g, 3.11 mmol) in DMF (10 mL). Add 60% NaH in mineral oil (124 mg, 3.11 mmol) and stir for 10 min. Then add methanesulfonic acid 1-methyl-piperidin-3-yl ester (1.80 g, 9.30 mmol) dissolved in DMF (5 mL). Heat the reaction to 80° C. for 19 h. Cool to rt and add ethyl acetate (50 mL) and water (50 mL). Separate the organic layer and wash with water (2×25 mL), then brine (25 mL). Collect the organic layer, dry over MgSO4, filter, and concentrate in vacuo. Chromatograph (silica gel, eluting with 0-10% 2M NH3 in MeOH:DCM, then 10% 2M NH3 in MeOH:DCM) to yield 445 mg (49%) of the title compound: mass spectrum (ion-spray): (m/z)=291.3 (M+1).

Workup

  1. washAdd DCM (10 mL) and wash the organic layer with 1N NaOH (20 mL)
  2. customCollect the organic layer
  3. dry with materialdry over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. stirringstir for 10 min
  7. temperatureHeat
  8. customthe reaction to 80° C. for 19 h
  9. temperatureCool to rt
  10. customSeparate the organic layer
  11. washwash with water (2×25 mL)
  12. customCollect the organic layer
  13. dry with materialdry over MgSO4
  14. filtrationfilter
  15. concentrationconcentrate in vacuo
  16. washChromatograph (silica gel, eluting with 0-10% 2M NH3 in MeOH

Sources & evidence

ORD record
ord-03478d3d5eb74b23b362d2432867a235
Source dataset
uspto-grants-2010_11
Patent number
US07838543B2

Reaction notes

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