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Sodium Carbonate → Benzyl (1R)-1-{[[2-(2,3-difluorophenyl)prop-2-enyl](2,4-dimethoxybenzyl)amino]carbonyl]but-3-enylcarbamate

HRID 20129
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HRID 20129 반응식
Br[C:2](=[CH2:33])[CH2:3][N:4]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=1[O:31][CH3:32])[C:5]([C@H:7]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:8][CH:9]=[CH2:10])=[O:6].[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1[C:2](=[CH2:33])[CH2:3][N:4]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=1[O:31][CH3:32])[C:5]([C@H:7]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:8][CH:9]=[CH2:10])=[O:6]
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참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 23657090Benzyl (1R)-1-{[(2-bromoprop-2-enyl)(2,4-dimethoxybenzyl)amino]carbonyl}but-3-enylcarbamate

생성물 1

HCID 86595035Benzyl (1R)-1-{[[2-(2,3-difluorophenyl)prop-2-enyl](2,4-dimethoxybenzyl)amino]carbonyl]but-3-enylcarbamate수율 69.4%

시약·촉매·용매 2

HCID 178418807
HCID 178418807, 화합물
촉매
HCID 6228Dimethylformamide용매

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온도
75 °C

실험 절차

Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium dichloromethane adduct (0.726 g, 0.889 mmol) was added to a solution of benzyl (1R)-1-{[(2-bromoprop-2-enyl)(2,4-dimethoxybenzyl)amino]carbonyl}but-3-enylcarbamate (9.2 g, 17.8 mmol), 2,3-difluorophenylboronic acid (2.95 g, 18.7 mmol) and sodium carbonate (2M in water; 19.6 mL, 39.1 mmol) in N,N-dimethylformamide (60 mL) and the mixture was heated to 75° C. After 2 h, the mixture was allowed to cool to ambient temperature and extracted with dichloromethane (3×). The combined organic extracts were washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (5% ethyl acetate/hexanes→55% ethyl acetate/hexanes) gave the title compound (6.8 g). MS 551.2 (M+1).

후처리

  1. temperatureto cool to ambient temperature
  2. extractionextracted with dichloromethane (3×)
  3. washThe combined organic extracts were washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (5% ethyl acetate/hexanes→55% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-f4958fc0ea414fc88c92d737760fc112
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07745427B2

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