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

HRID 1793053Notes

Reaction equation

HRID 1793053 reaction equation
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]

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 86590726HCID 86590726, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

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 (1H, m), 6.84–6.95 (3H, m), 6.76–6.79 (1H, m), 3.91–3.94 (1H, m), 3.81–3.85 (2H, m), 3.53–3.55 (2H, m), 2.57 (2H, q, J=15.1, 7.6 Hz), 1.19 (3H, 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).

Workup

  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

Sources & evidence

ORD record
ord-7c280b71af1a4325818d2a3341d881cc
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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