Water → (2R)-4-{4'-[(5R)-5-(acetamidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2'-fluorobiphenyl-4-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533560노트

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HRID 533560 반응식
C(=O)([O-])[O-].[K+].[K+].CC1(C)COB([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22][C:21]3=[O:30])=[CH:16][C:15]=2[F:31])OC1.Br[C:34]1[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][C@@:42]([CH3:57])([S:53]([CH3:56])(=[O:55])=[O:54])[C:43]([NH:45][O:46][CH:47]2[CH2:52][CH2:51][CH2:50][CH2:49][O:48]2)=[O:44])=[CH:36][CH:35]=1.O>O1CCOCC1.[Pd+2]>[C:27]([NH:26][CH2:25][C@H:23]1[O:22][C:21](=[O:30])[N:20]([C:17]2[CH:18]=[CH:19][C:14]([C:34]3[CH:35]=[CH:36][C:37]([CH2:40][CH2:41][C@@:42]([CH3:57])([S:53]([CH3:56])(=[O:54])=[O:55])[C:43]([NH:45][O:46][CH:47]4[CH2:52][CH2:51][CH2:50][CH2:49][O:48]4)=[O:44])=[CH:38][CH:39]=3)=[C:15]([F:31])[CH:16]=2)[CH2:24]1)(=[O:29])[CH3:28]

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 56950324(2R)-4-(4-bromophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideHCID 66577981N-({(5S)-3-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide

생성물 1

HCID 86668777(2R)-4-{4'-[(5R)-5-(acetamidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2'-fluorobiphenyl-4-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

시약·촉매·용매 2

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

Palladium (II) EnCat (230 mg, 0.07 mmol) was added to a mixture of potassium carbonate (207 mg, 1.5 mmol), N-({(5S)-3-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (234 mg, 0.644 mmol), and 111a (2R)-4-(4-bromophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide which was prepared as in Preparation 7 (200 mg, 0.46 mmol) in dioxane:water (6 mL, 5:1) in a 20 mL sealed vial. The vial was heated overnight at 90° C. The reaction was cooled to ambient temperature, filtered through celite and the filtrate was washed with ethyl acetate (30 mL) and methanol (15 mL). The combined organics were concentrated in vacuo and purified by chromatography on silica gel (gradient: 80:20 heptanes:ethyl acetate to 0:100 heptanes:ethyl acetate, followed by ethyl acetate:methanol 90:10) to furnish the title compound as a light brown gum. Yield 50 mg, 18% theoretical yield. LCMS m/z 604.3 (M−1)

후처리

  1. temperatureThe reaction was cooled to ambient temperature
  2. filtrationfiltered through celite
  3. washthe filtrate was washed with ethyl acetate (30 mL) and methanol (15 mL)
  4. concentrationThe combined organics were concentrated in vacuo
  5. custompurified by chromatography on silica gel (gradient: 80:20 heptanes:ethyl acetate to 0:100 heptanes:ethyl acetate, followed by ethyl acetate:methanol 90:10)

출처 및 근거

ORD 기록
ord-e64ab839770043e8b40b7492266e2bc8
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853258B2

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