p-Toluenesulfonic acid → N-[(R)-2,3-dihydroxy-propoxy]-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide

HRID 2181483ノート

反応式

HRID 2181483 の反応式
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10](=[O:29])[C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[C:12]=2[NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH3:27])=[CH:22][C:21]=2[F:28])[CH2:4][O:3]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.O>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10](=[O:29])[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[C:12]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH3:27])=[CH:22][C:21]=1[F:28]

参加物

5

反応物 2

HCID 6101p-Toluenesulfonic acidHCID 86590726N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide

生成物 1

HCID 10215923N-[(R)-2,3-dihydroxy-propoxy]-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide収率 94.4%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

To a stirring solution of the product of Example 31, Step E, N-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide (0.515 g, 1.213 mmol) in methanol (10 mL) and water (1 mL) was added p-toluenesulfonic acid (0.115 g, 0.607 mmol). After stirring for 17 hours the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed twice saturated sodium carbonate solution and twice with brine. The organic layer was collected, dried over sodium sulfate, filtered and concentrated in vacuo to afford N-[(R)-2,3-dihydroxy-propoxy]-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide (0.440 g, 94.4%) as a clear oil/foam. 1NMR (400 MHz; CD3OD) δ 7.35 (1 H, m), 6.84-6.95 (3 H, m), 6.76-6.79 (1 H, m), 3.91-3.94 (1 H, m), 3.81-3.85 (2 H, m), 3.53-3.55(2 H, m), 2.57(2 H, q, J=15.1, 7.6 Hz), 1.19(3 H, t, J=7.6 Hz); 19F-NMR (376 MHz; CD3OD) δ −132.3, −134.8, −147.3; MS(APCI+)=385; Anal. calcd/found for C18H19F3N2O4: C, 56.25/56.22; H, 4.98/4.93; N, 7.29/7.17; [α]25D −5.6° (c 10.8, EtOH).

後処理

  1. customwas partitioned between ethyl acetate and water
  2. washThe organic layer was washed twice saturated sodium carbonate solution
  3. customThe organic layer was collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-33ca859e4a084f76b885f54edfb6c138
出典データセット
uspto-grants-2005_05
特許番号
US06891066B2

反応ノート

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