Sodium hydride → HCID 86718536, compound

HRID 929954Notes

Reaction equation

HRID 929954 reaction equation
[CH3:1][C@H:2]1[C@H:6]([C:7]2[S:8][CH:9]=[CH:10][N:11]=2)[O:5][C:4](=[O:12])[NH:3]1.[H-].[Na+].[Cl:15][C:16]1[CH:21]=[C:20](Cl)[N:19]=[C:18]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:17]=1>CN(C=O)C>[Cl:15][C:16]1[N:17]=[C:18]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:19]=[C:20]([N:3]2[C@@H:2]([CH3:1])[C@H:6]([C:7]3[S:8][CH:9]=[CH:10][N:11]=3)[O:5][C:4]2=[O:12])[CH:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholineHCID 68076180HCID 68076180, compound

Product 1

HCID 86718536HCID 86718536, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

(4S,5R)-4-Methyl-5-thiazol-2-yl-oxazolidin-2-one (4.70 g, 20.1 mmol) was dissolved in 70 mL of DMF and cooled to 0° C. NaH (964 mg, 60% in oil, 24.1 mmol) was added under argon, and the reaction mixture was stirred for 30 minutes at 0° C. 4-(4,6-dichloropyrimidin-2-yl)morpholine (3.70 g, 20.1 mmol) dissolved in 30 mL of DMF was added, and the reaction mixture was stirred for 3 hours at 0° C., followed by stirring at RT for 2 hours. The reaction was then quenched by addition of aqueous NH4Cl, followed by dilution with EtOAc; the organic solvents were separated, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography (80 g SiO2) using EtOAc in hexane from 0% to 100% in order to give the title compound (3.64 g, 48%). LC-MS: [M+H] 382.2, 384.1; Rt 1.10 min; (LCMS method 1). 1H NMR (400 MHz, CHCl3-d): 7.77 (d, 1H), 7.38-7.33 (m, 2H), 5.39 (d, 1H), 5.07-4.98 (m, 1H), 3.75-3.55 (m, 8H), 1.64 (d, 3H).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred for 3 hours at 0° C.
  3. stirringby stirring at RT for 2 hours
  4. customThe reaction was then quenched by addition of aqueous NH4Cl
  5. customthe organic solvents were separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (80 g SiO2)

Sources & evidence

ORD record
ord-fa22bb2390d7430aa6feb9352d7984a9
Source dataset
uspto-grants-2016_03
Patent number
US09296733B2

Reaction notes

Loading…