Hydrochloric Acid → 2-(4-Fluoro-benzenesulfonyl)-2-aza-spiro[3.3]heptane

HRID 238585

反応式

HRID 238585 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:15][C:16]1([CH2:20]Br)[CH2:19]O[CH2:17]1.Cl.[CH3:23]N(C)C=O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]2[CH2:17][C:16]3([CH2:20][CH2:23][CH2:19]3)[CH2:15]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1

参加物

6

反応物 5

HCID 313Hydrochloric AcidHCID 6228Dimethylformamide2 回HCID 24758Sodium hydrideHCID 75464Oxetane, 3,3-bis(bromomethyl)-HCID 1202314-Fluorobenzenesulfonamide

生成物 1

HCID 673047502-(4-Fluoro-benzenesulfonyl)-2-aza-spiro[3.3]heptane収率 26%

反応条件

温度
0 °C

実験手順

To a cooled (ice-water bath) solution of 4-fluoro-benzenesulfonamide (320 mg, 1.83 mmol) in N,N-dimethylformamide (5 mL), was added sodium hydride (150 mg, 60% dispersion, 3.75 mmol) portion-wise. After the mixture was stirred at 0° C. for 10 minutes, a solution of 3,3-bis-bromomethyl-oxetane (440 mg, 1.8 mmol) in N,N-dimethylformamide (3 mL) was added. The resulting mixture was stirred at room temperature overnight, then neutralized with 1 N hydrochloric acid, and extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with brine (20 mL×3), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (elution with 20% ethyl acetate in petroleum ether) to afford 2-(4-fluoro-benzenesulfonyl)-2-aza-spiro[3.3]heptane (120 mg, 26%) as a white solid (reference: Blizzard T. A. et al., Bioorg. Med. Chem. Lett. 14 (2004) 3861-3864), MS cald, for C12H14FNO2S 255, obsd. (ESI+) [(M+H)+] 256.

後処理

  1. stirringThe resulting mixture was stirred at room temperature overnight
  2. extractionextracted with ethyl acetate (20 mL×3)
  3. washThe combined organic layers were washed with brine (20 mL×3)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography (elution with 20% ethyl acetate in petroleum ether)

出典と根拠

ORDレコード
ord-7460e9efcd8f4cdb9cc383ca0710b96f
出典データセット
uspto-grants-2014_02
特許番号
US08642629B2

関連ノート

読み込み中…