Sodium hydride → (11S)-11-{[(4-fluorobenzyl)oxy]methyl}-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

HRID 221602Notes

Reaction equation

HRID 221602 reaction equation
[H-].[Na+].[OH:3][CH2:4][C@@H:5]1[N:10]2[C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[CH:13][C:12]=3[N:21]=[C:9]2[CH2:8][O:7][CH2:6]1.[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=1.C([O-])(O)=O.[Na+]>C(OCC)(=O)C>[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][O:3][CH2:4][C@@H:5]2[N:10]3[C:11]4[C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:14]=[CH:13][C:12]=4[N:21]=[C:9]3[CH2:8][O:7][CH2:6]2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 516892Sodium BicarbonateHCID 67156623(11S)-11-hydroxymethyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

Product 1

HCID 67157059(11S)-11-{[(4-fluorobenzyl)oxy]methyl}-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolineYield 98.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 100-mL, round-bottomed flask, under an atmosphere of N2, was charged with sodium hydride (60% oil dispersion, 72 mg, 1.78 mmol). The sodium hydride was washed with 3 portions of hexanes to remove the oil and then 20 mL of anhydrous THF was added. The reaction mixture was cooled to 0° C. and (11S)-11-hydroxymethyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline (413 mg, 1.62 mmol) was added. After stirring for 75 minutes, 4-fluorobenzyl bromide (215 μL, 1.78 mmol) was added. The reaction was allowed to warm to ambient temperature overnight. After 20 hours the reaction mixture was treated with 20 mL of saturated NaHCO3 solution and 20 mL of ethyl acetate and the layers were separated. The organic portion was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated under reduce pressure to give (11S)-11-{[(4-fluorobenzyl)oxy]methyl}-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline (580 mg) as a light-yellow, glassy solid.

Workup

  1. washThe sodium hydride was washed with 3 portions of hexanes
  2. customto remove the oil
  3. addition20 mL of anhydrous THF was added
  4. temperatureto warm to ambient temperature overnight
  5. customthe layers were separated
  6. washThe organic portion was washed with H2O and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-997cc1059a1541f68fb74c0b13b8a74c
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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