Hydrochloric Acid → 2-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanol

HRID 1972446노트

반응식

HRID 1972446 반응식
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:14])([CH3:13])[C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][C:3]=1[N:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1.Cl.O1CCOCC1.C(N(CC)CC)C.[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[S:47](Cl)(=[O:49])=[O:48]>CCOC(C)=O>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:14])([CH3:13])[C:9]([F:10])([F:12])[F:11])[CH:5]=[CH:4][C:3]=1[N:15]1[CH2:16][CH2:17][N:18]([S:47]([C:43]2[S:42][CH:46]=[CH:45][CH:44]=2)(=[O:49])=[O:48])[CH2:19][CH2:20]1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 855182-Thiophenesulfonyl chlorideHCID 66582356Tert-butyl 4-(2-bromo-4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinecarboxylate

생성물 1

HCID 665829132-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanol수율 67.5%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A 250 mL round-bottomed flask was charged with tert-butyl 4-(2-bromo-4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinecarboxylate (3.70 g, 8.16 mmol), 25 mL of EtOAc, and 8 mL of 4M HCl in dioxane (32 mmol). After heating at reflux for 30 min, the mixture was cooled and concentrated. The resulting viscous oil was dissolved in 30 mL of CH2Cl2 and triethylamine (3.98 mL, 28.6 mmol). At 0° C., 2-thiophenesulfonyl chloride (1.49 g, 8.16 mmol, Sigma-Aldrich, St. Louis, Mo.) was added at 0° C. After 15 min, the mixture was concentrated then re-dissolved in 5 mL of CH2Cl2, filtered, and purified via column chromatography (120 g of silica, 0 to 50% EtOAc in hexanes) to give 2-(3-bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1-trifluoro-2-propanol (2.75 g) as a white solid.

후처리

  1. temperatureAfter heating
  2. temperatureat reflux for 30 min
  3. temperaturethe mixture was cooled
  4. concentrationconcentrated
  5. dissolutionThe resulting viscous oil was dissolved in 30 mL of CH2Cl2
  6. concentrationthe mixture was concentrated
  7. dissolutionthen re-dissolved in 5 mL of CH2Cl2
  8. filtrationfiltered
  9. custompurified via column chromatography (120 g of silica, 0 to 50% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-9550fbd33772405bbd691f43f9f7b2a4
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431563B2

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