Sodium hydride → HCID 44627113, compound

HRID 1496897Notes

Reaction equation

HRID 1496897 reaction equation
[N+]([C:4]1[NH:5][CH:6]=[C:7]([N+:9]([O-:11])=[O:10])[N:8]=1)([O-])=O.[CH2:12]([O:16][Si](C(C)(C)C)(C)C)[C@H:13]1[O:15][CH2:14]1.Br[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][C:33]=2[Cl:43])=[CH:28][CH:27]=1.[H-].[Na+]>CN(C=O)C>[Cl:43][C:33]1[CH:34]=[C:35]([O:38][C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:37][C:32]=1[C:29]1[CH:30]=[CH:31][C:26]([CH2:25][O:15][C@@H:13]2[CH2:12][O:16][C:4]3=[N:8][C:7]([N+:9]([O-:11])=[O:10])=[CH:6][N:5]3[CH2:14]2)=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 10954307(S)-Glycidoxy-t-butyldimethylsilaneHCID 44627769HCID 44627769, compoundHCID 178526857HCID 178526857, compound

Product 1

HCID 44627113HCID 44627113, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-01 (41) (reported in U.S. Pat. No. 5,668,127 via 4 steps, starting from 2,4-dinitroimidazole and tert-butyldimethylsilyl (S)-glycidyl ether) (342 mg, 1.85 mmol) and bromide 39 (741 mg, 2.03 mmol) in anhydrous DMF (7 mL) under N2 at 0° C. was treated with 60% NaH (111 mg, 2.78 mmol), then quickly degassed and resealed under N2. After stirring at room temperature for 3 h, the reaction was cooled (CO2/acetone), quenched with ice/aqueous NaHCO3 (20 mL), added to brine (80 mL) and extracted with CH2Cl2 (6×80 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel, eluting with CH2Cl2, to give 1 (694 mg, 80%) as a light yellow solid: mp (CH2Cl2/pentane) 80-82° C.; 1H NMR (CDCl3) δ 7.45-7.35 (m, 6H), 7.34 (d, J=8.5 Hz, 1H), 7.20 (m, 1H), 4.79 (d, J=12.0 Hz, 1H), 4.68 (d, J=12.1 Hz, 1H), 4.65 (ddd, J=12.1, 2.9, 2.5 Hz, 1H), 4.37 (br d, J=11.8 Hz, 1H), 4.24-4.12 (m, 3H). Anal. (C20H15ClF3N3O5) C, H, N.

Workup

  1. customat 0° C.
  2. customquickly degassed
  3. temperaturethe reaction was cooled (CO2/acetone)
  4. customquenched with ice/aqueous NaHCO3 (20 mL)
  5. additionadded to brine (80 mL)
  6. extractionextracted with CH2Cl2 (6×80 mL)
  7. customThe combined extracts were evaporated to dryness
  8. customthe residue was chromatographed on silica gel
  9. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-92ab2b5055694f0d9596f47eb829e4b7
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

Loading…