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 533560ノート

反応式

HRID 533560 の反応式
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]

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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)

後処理

  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)

出典と根拠

ORDレコード
ord-e64ab839770043e8b40b7492266e2bc8
出典データセット
uspto-grants-2014_10
特許番号
US08853258B2

反応ノート

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