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 400640노트

반응식

HRID 400640 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 25517Ammonium Chloride용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-daf539d9f83443c7a951f3d31d19b30e
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741897B2

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