Magnesium Bromide → 6-Benzyloxy-2-[3-t-butyldimethylsilyloxymethyl-4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-Methoxy-4-(1-pyrrolidinylmethyl)phenyl Ketone

HRID 1387120노트

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HRID 1387120 반응식
[Si:1]([O:8][CH2:9][C:10]1[CH:23]=[C:22](Br)[CH:21]=[CH:20][C:11]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[Mg+2].[Br-].[Br-].[CH3:33][O:34][C:35]1[CH:36]=[C:37]([C:48]([C:50]2[C:51]3[CH:61]=[CH:60][C:59]([O:62][CH2:63][C:64]4[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=4)=[CH:58][C:52]=3[S:53][C:54]=2N(C)C)=[O:49])[CH:38]=[CH:39][C:40]=1[CH2:41][N:42]1[CH2:47][CH2:46]O[CH2:44][CH2:43]1>C1COCC1>[CH3:33][O:34][C:35]1[CH:36]=[C:37]([C:48]([C:50]2[C:51]3[CH:61]=[CH:60][C:59]([O:62][CH2:63][C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=4)=[CH:58][C:52]=3[S:53][C:54]=2[C:22]2[CH:21]=[CH:20][C:11]([O:12][CH2:13][CH2:14][N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:23]=2)=[O:49])[CH:38]=[CH:39][C:40]=1[CH2:41][N:42]1[CH2:43][CH2:44][CH2:46][CH2:47]1

참가 물질

6

반응물 4

HCID 82241Magnesium BromideHCID 211829811-[2-(2-t-Butyldimethylsilyloxymethyl-4-bromophenoxy)ethyl]pyrrolidineHCID 224627876-Benzyloxy-2-(dimethylamino)benzo[b]thiophen-3-yl 3-methoxy-4-[(4-morpholinyl)methyl]phenyl ketoneHCID 178418339Butyllithium

생성물 1

HCID 211827376-Benzyloxy-2-[3-t-butyldimethylsilyloxymethyl-4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 3-Methoxy-4-(1-pyrrolidinylmethyl)phenyl Ketone수율 11.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a solution of (142 mg, 0.343 mmol) 1-[2-(2-t-butyldimethylsilyloxymethyl-4-bromophenoxy)ethyl]pyrrolidine (Part B) in 15 mL of freshly distilled THF cooled to −78° C. was added 0.24 mL of n-BuLi. The solution was stirred at −78° C. for 1 h 20 min. To the solution was added 1.0 mL of freshly prepared MgBr2 (prepared by reacting 54 mL of dibromoethane with 13 mg of etched magnesium ribbon in 1.0 mL of THF) via cannula at −78° C. and stirred for 10 min. The ice bath was removed and the solution was stirred at room temperature for 30 min. The Grignard reagent was then added dropwise via a cannula to (177 mg, 0.343 mmol) 6-benzyloxy-2-(dimethylamino)benzo[b]thiophen-3-yl 3-methoxy-4-[(4-morpholinyl)methyl]phenyl ketone (Example 49, Part C) dissolved in 1.0 mL of THF at room temperature. The reaction was stirred for 5.5 h. The reaction was quenched by adding 4 mL of satd. NH4Cl solution. The mixture was then extracted with EtOAc (2×40 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. Purification by flash chromatography (silica gel, 46:46:8 CHCl3-Hexanes-2 M NH3 in MeOH) afforded 30.8 mg (0.0381 mmol, 11%) of a yellow foam.

후처리

  1. stirringstirred for 10 min
  2. customThe ice bath was removed
  3. stirringthe solution was stirred at room temperature for 30 min
  4. stirringThe reaction was stirred for 5.5 h
  5. customThe reaction was quenched
  6. additionby adding 4 mL of satd
  7. extractionThe mixture was then extracted with EtOAc (2×40 mL)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography (silica gel, 46:46:8 CHCl3-Hexanes-2 M NH3 in MeOH)

출처 및 근거

ORD 기록
ord-01a47d6e26074d15b6eccae47833f193
출처 데이터셋
uspto-grants-2001_07
특허 번호
US06265575B1

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