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1,1-Dichloroethane → (S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1751377
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HRID 1751377 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]3[C:16]4[CH:17]=[CH:18][C:19]([B:21]5[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]5)=[CH:20][C:15]=4[S:14][C:13]=3[CH:30]=2)O1.Br[C:33]1[CH:34]=[CH:35][C:36]2[N:40]=[C:39]([C@@H:41]3[CH2:45][CH2:44][CH2:43][N:42]3[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[NH:38][C:37]=2[CH:53]=1.C(=O)([O-])[O-].[K+].[K+].ClC(Cl)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.C(COC)OC>[CH3:27][C:24]1([CH3:26])[C:23]([CH3:28])([CH3:29])[O:22][B:21]([C:19]2[CH:18]=[CH:17][C:16]3[C:12]4[CH:11]=[CH:10][C:9]([C:33]5[CH:34]=[CH:35][C:36]6[N:40]=[C:39]([C@@H:41]7[CH2:45][CH2:44][CH2:43][N:42]7[C:46]([O:48][C:49]([CH3:51])([CH3:50])[CH3:52])=[O:47])[NH:38][C:37]=6[CH:53]=5)=[CH:30][C:13]=4[S:14][C:15]=3[CH:20]=2)[O:25]1
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참가 물질

8

반응물 4

HCID 63651,1-DichloroethaneHCID 11430Potassium CarbonateHCID 56605032(S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylateHCID 676817643,7-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzothiophene

생성물 1

HCID 67681976(S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate
수율 62.2%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 1140Toluene용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of 3,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-dibenzo[b,d]thiophene (3.6 g, 8.2 mmol), (S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (1.0 g, 2.7 mmol), tetrakis(triphenylphosphine)palladium(0) (0.31 mg, 0.27 mmol), 2M aqueous potassium carbonate solution (5 mL, 10 mmol), dimethoxyethane (25 mL), toluene (5 mL) and dichloroethane (2.5 mL) was degassed under a stream of argon for 15 minutes. The reaction was heated to 85° C. for 2 hours. Upon completion, the reaction was cooled to room temperature, diluted with ethyl acetate and filtered through Celite. The filtrate was washed with water and brine, dried (MgSO4) and concentrated. The resulting crude material was purified by flash column chromatography to yield (S)-tert-butyl 2-(6-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dibenzo[b,d]thiophen-3-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate (1.0 g, 62%).

후처리

  1. customwas degassed under a stream of argon for 15 minutes
  2. temperatureUpon completion, the reaction was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through Celite
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe resulting crude material was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-933b68e1cd6e41858449711bde398393
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09156823B2

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