Sodium hydride → HCID 66956004, compound

HRID 2066648Notes

Reaction equation

HRID 2066648 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[N:6][CH:7]=1.[N+:9]([C:12]1[N:13]=[C:14]2[N:19]([CH:20]=1)[CH2:18][CH2:17][CH:16]([CH2:21][OH:22])[O:15]2)([O-:11])=[O:10].[H-].[Na+].C(=O)=O.CC(C)=O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH2:21][CH:16]2[O:15][C:14]3=[N:13][C:12]([N+:9]([O-:11])=[O:10])=[CH:20][N:19]3[CH2:18][CH2:17]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 27831685-Bromo-2-fluoropyridine2×HCID 18522661Acetone cardiceHCID 66956832HCID 66956832, compound

Product 1

HCID 66956004HCID 66956004, compoundYield 87.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Bromo-2-fluoropyridine (91) (0.52 mL, 5.05 mmol) was added to a solution of oxazine alcohol 134 (see Example 2BB) (500 mg, 2.51 mmol) in anhydrous DMF (10 mL) under N2 at 0° C. The resulting mixture was treated with 60% NaH (151 mg, 3.78 mmol), then quickly degassed and resealed under N2. Further 5-bromo-2-fluoropyridine (91) (0.52 mL, 5.05 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 (30 mL), added to brine (100 mL) and extracted with CH2Cl2 (8×100 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-1% EtOAc/CH2Cl2 firstly gave foreruns, and then further elution with 2-4% EtOAc/CH2Cl2 gave 7-{[(5-bromo-2-pyridinyl)oxy]methyl}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (136) (778 mg, 87%) as a white solid: mp (MeOH/CH2Cl2/hexane) 182-184° C.; 1H NMR [(CD3)2SO] δ 8.30 (dd, J=2.6, 0.5 Hz, 1H), 8.07 (s, 1H), 7.95 (dd, J=8.8, 2.6 Hz, 1H), 6.91 (dd, J=8.8, 0.6 Hz, 1H), 4.90 (m, 1H), 4.58 (dd, J=12.0, 3.3 Hz, 1H), 4.52 (dd, J=12.0, 6.0 Hz, 1H), 4.17 (ddd, J=12.6, 5.8, 2.8 Hz, 1H), 4.09 (ddd, J=12.5, 11.0, 5.2 Hz, 1H), 2.34-2.26 (m, 1H), 2.23-2.11 (m, 1H). Anal. (C12H11BrN4O4) C, H, N.

Workup

  1. customquickly degassed
  2. customquenched with ice/aqueous NaHCO3 (30 mL)
  3. additionadded to brine (100 mL)
  4. extractionextracted with CH2Cl2 (8×100 mL)
  5. customThe combined extracts were evaporated to dryness
  6. customthe residue was chromatographed on silica gel
  7. washElution with 0-1% EtOAc/CH2Cl2 firstly gave foreruns
  8. washfurther elution with 2-4% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-c479caebba604a699701969f78f8e597
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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