Dimethylamine → 7-[2-(2,2-Dimethyl-4-trifluoromethyl-[1,3]dioxolan-4-yl)-1,1-dimethyl-ethyl]-2,3-dihydrobenzofuran-5-sulfonic acid dimethylamide

HRID 400640ノート

反応式

HRID 400640 の反応式
Br[C:2]1[CH:3]=[C:4]([C:11]([CH3:25])([CH3:24])[CH2:12][C:13]2([C:20]([F:23])([F:22])[F:21])[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[O:14]2)[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[Li]CCCC.Cl[N:32]1[C:36](=O)CC[C:33]1=O.[S:39](Cl)(Cl)(=[O:41])=[O:40].CNC>C1COCC1.[Cl-].[NH4+]>[CH3:33][N:32]([CH3:36])[S:39]([C:2]1[CH:3]=[C:4]([C:11]([CH3:25])([CH3:24])[CH2:12][C:13]2([C:20]([F:23])([F:22])[F:21])[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[O:14]2)[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1)(=[O:41])=[O:40]

参加物

8

反応物 5

HCID 674DimethylamineHCID 24648Sulfuryl chlorideHCID 31398ChlorosuccinimideHCID 578099225-Bromo-7-[2-(2,2-dimethyl-4-trifluoromethyl-[1,3]dioxolan-4-yl)-1,1-dimethylethyl]-2,3-dihydrobenzofuranHCID 178418339Butyllithium

生成物 1

HCID 600263797-[2-(2,2-Dimethyl-4-trifluoromethyl-[1,3]dioxolan-4-yl)-1,1-dimethyl-ethyl]-2,3-dihydrobenzofuran-5-sulfonic acid dimethylamide収率 83%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 25517Ammonium Chloride溶媒

実験手順

A solution of 5-bromo-7-[2-(2,2-dimethyl-4-trifluoromethyl-[1,3]dioxolan-4-yl)-1,1-dimethylethyl]-2,3-dihydrobenzofuran (4.0 g, 9.4 mmol) in 8 mL of THF was treated with n-BuLi (2.5 M in hexanes, 4.2 mL, 10.5 mmol) at −78° C. After 15 minutes, an excess of SO2 gas was bubbled into the mixture and the reaction was monitored for the disappearance of the starting material. Next, the reaction mixture was concentrated under a stream of nitrogen gas, diluted with THF, and treated with N-chlorosuccinimide (1.48 g, 11.1 mmol). The mixture was stirred for 15 minutes and divided into three equal portions. A stock solution of sulfonyl chloride (⅓ of the mixture) in 8 mL of THF was treated with dimethylamine (2 M in THF, 10 mL, 20 mmol). After 30 minutes, the mixture was diluted with 20 mL of saturated aqueous ammonium chloride solution and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of saturated aqueous ammonium chloride solution, two 10 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified on silica gel (3% to 30% ethyl acetate in hexanes, gradient) to afford 1.18 g (83% yield) of 7-[2-(2,2-dimethyl-4-trifluoromethyl-[1,3]dioxolan-4-yl)-1,1-dimethyl-ethyl]-2,3-dihydrobenzofuran-5-sulfonic acid dimethylamide, which was used without further purification.

後処理

  1. customan excess of SO2 gas was bubbled into the mixture
  2. concentrationNext, the reaction mixture was concentrated under a stream of nitrogen gas
  3. additiondiluted with THF
  4. waitAfter 30 minutes
  5. extractionextracted with three 10 mL portions of ethyl acetate
  6. washThe combined organic layers were washed with three 10 mL portions of saturated aqueous ammonium chloride solution, two 10 mL portions of brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified on silica gel (3% to 30% ethyl acetate in hexanes, gradient)

出典と根拠

ORDレコード
ord-daf539d9f83443c7a951f3d31d19b30e
出典データセット
uspto-grants-2014_06
特許番号
US08741897B2

反応ノート

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