Cesium carbonate → N-(2,4-dimethylphenyl)-3,5-difluoro-N-isobutyl-4-vinylbenzenesulfonamide

HRID 1487062노트

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HRID 1487062 반응식
[B-](F)(F)(F)[CH:2]=[CH2:3].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:28]1[C:33]([F:34])=[CH:32][C:31]([S:35]([N:38]([C:43]2[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][C:44]=2[CH3:50])[CH2:39][CH:40]([CH3:42])[CH3:41])(=[O:37])=[O:36])=[CH:30][C:29]=1[F:51].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.O.[Pd](Cl)Cl>[CH3:50][C:44]1[CH:45]=[C:46]([CH3:49])[CH:47]=[CH:48][C:43]=1[N:38]([CH2:39][CH:40]([CH3:42])[CH3:41])[S:35]([C:31]1[CH:32]=[C:33]([F:34])[C:28]([CH:2]=[CH2:3])=[C:29]([F:51])[CH:30]=1)(=[O:37])=[O:36]

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 23679353Potassium vinyltrifluoroborate2회HCID 898759904-bromo-N-(2,4-dimethylphenyl)-3,5-difluoro-N-isobutylbenzenesulfonamide

생성물 1

HCID 89875754N-(2,4-dimethylphenyl)-3,5-difluoro-N-isobutyl-4-vinylbenzenesulfonamide

시약·촉매·용매 4

HCID 24290Palladium Chloride촉매HCID 962Water용매3회HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

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온도
140 °C

실험 절차

To a vial was added potassium trifluoro(vinyl)borate (0.744 g, 5.55 mmol), triphenylphosphine (0.073 g, 0.278 mmol), 4-bromo-N-(2,4-dimethylphenyl)-3,5-difluoro-N-isobutylbenzenesulfonamide (2 g, 4.63 mmol) suspension in tetrahydrofuran (THF) (22 mL), cesium carbonate (4.52 g, 13.88 mmol), water (2.200 mL) and palladium(II) chloride (0.016 g, 0.093 mmol). The mixture was divided evenly between two microwave vials and the vessels then sealed and heated by microwaves (Biotage Initiator) to 140° C. for 30 minutes. LCMS analysis showed some conversion, so additional 0.5 equivalent of potassium trifluoro(vinyl)borate was added to each reaction, along with extra water (2 mL) and THF (2 mL). The reactions were reheated by microwaves for a further 1 hour at 140° C. The reactions were then diluted with dichloromethane (5 mL) and water (2 mL), filtered through celite and dried using a hydrophobic frit. The organics were concentrated and purified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient). The appropriate fractions were combined and evaporated in vacuo to give two batches of the required product, 769 mg and 856 mg, as yellow oils. LCMS [LCMS2] Rt 1.60 min, m/z (ES+) 380 (M+H).

후처리

  1. customthe vessels then sealed
  2. filtrationfiltered through celite
  3. customdried
  4. concentrationThe organics were concentrated
  5. custompurified by flash silica (Si) chromatography (0-25% ethyl acetate-cyclohexane gradient)
  6. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-18a993b94ba04b60ba6fb44a910eab14
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09428452B2

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