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 549170ノート

反応式

HRID 549170 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-de3a3ea3011340429eb9bf92a08abbbc
出典データセット
uspto-grants-2011_05
特許番号
US07943609B2

反応ノート

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