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

HRID 2181483노트

반응식

HRID 2181483 반응식
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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-33ca859e4a084f76b885f54edfb6c138
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06891066B2

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