Sodium hydride → HCID 66956518, compound

HRID 2066657Notes

Reaction equation

HRID 2066657 reaction equation
[CH3:1][C:2]1([CH2:14][OH:15])[O:7][C:6]2=[N:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][N:5]2[CH2:4][CH2:3]1.[H-].[Na+].[Br:18][C:19]1[CH:20]=[CH:21][C:22](F)=[N:23][CH:24]=1.C(=O)=O.CC(C)=O>CN(C=O)C>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([O:15][CH2:14][C:2]2([CH3:1])[O:7][C:6]3=[N:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][N:5]3[CH2:4][CH2:3]2)=[N:23][CH:24]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 27831685-Bromo-2-fluoropyridineHCID 18522661Acetone cardiceHCID 66955363HCID 66955363, compound

Product 1

HCID 66956518HCID 66956518, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of alcohol 149 (200 mg, 0.938 mmol) in anhydrous DMF (4 mL) under N2 at 0° C. was treated with 60% NaH (53.8 mg, 1.35 mmol), then quickly degassed and resealed under N2. 5-Bromo-2-fluoropyridine (91) (0.245 mL, 2.38 mmol) was added and the mixture was stirred at room temperature for 2.5 h, and then cooled (CO2/acetone), quenched with ice/aqueous NaHCO3 (10 mL), added to brine (40 mL), and extracted with CH2Cl2 (10×50 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with CH2Cl2 firstly gave foreruns, and then further elution with 1-3% EtOAc/CH2Cl2 gave 7-{[(5-bromo-2-pyridinyl)oxy]methyl}-7-methyl-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (150) (269 mg, 78%) as a cream solid: mp (CH2Cl2/pentane) 172-174° C.; 1H NMR (CDCl3) δ 8.17 (br d, J=2.2 Hz, 1H), 7.67 (dd, J=8.8, 2.5 Hz, 1H), 6.64 (dd, J=8.7, 0.4 Hz, 1H), 4.49 (d, J=11.5 Hz, 1H), 4.42 (d, J=11.4 Hz, 1H), 4.17 (dt, J=12.7, 6.1 Hz, 1H), 4.09 (ddd, J=12.6, 7.7, 5.8 Hz, 1H), 2.45 (ddd, J=14.5, 7.6, 5.9 Hz, 1H), 2.18 (dt, J=14.6, 6.1 Hz, 1H), 1.57 (s, 3H). Anal. (C13H13BrN4O4) C, H, N.

Workup

  1. customquickly degassed
  2. customquenched with ice/aqueous NaHCO3 (10 mL)
  3. additionadded to brine (40 mL)
  4. extractionextracted with CH2Cl2 (10×50 mL)
  5. customThe combined extracts were evaporated to dryness
  6. customthe residue was chromatographed on silica gel
  7. washElution with CH2Cl2 firstly gave foreruns
  8. washfurther elution with 1-3% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-4d661f2720de48da8659a01b27177bdf
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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