Hydrochloric Acid → 2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-1-hydroxymethyl-ethoxy)-benzamide

HRID 1793059Notes

Reaction equation

HRID 1793059 reaction equation
CC1(C)[O:7][CH2:6][CH:5]([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.Cl>C(O)C>[CH2:26]([C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:12]2[C:13]([F:18])=[C:14]([F:17])[CH:15]=[CH:16][C:11]=2[C:10]([NH:9][O:8][CH:5]([CH2:6][OH:7])[CH2:4][OH:3])=[O:29])=[C:21]([F:28])[CH:22]=1)[CH3:27]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22025657N-(2,2-Dimethyl-[1,3]dioxan-5-yloxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide

Product 1

HCID 101940342-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-1-hydroxymethyl-ethoxy)-benzamideYield 84.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirring solution of the product of Example 33, Step C, N-(2,2-dimethyl-[1,3]dioxan-5-yloxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide (0.416 g, 0.980 mmol) in ethanol (5 mL) was added 1 molar aqueous hydrochloric acid solution (1 mL). After stirring for 1 hour at ambient temperature the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed twice with water and twice with brine. The organic layer was collected, dried over sodium sulfate, filtered and concentrated in vacuo. The affording foam was crystallized in ethyl acetate and heptane to afford 2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-1-hydroxymethyl-ethoxy)-benzamide (0.318 g, 84.6%) as a white crystalline solid: m.p. 91–93° C.; 1NMR (400 MHz; CD3OD) δ 7.38 (1H, t, J=6.8 Hz), 6.85–6.96 (3H, m), 6.73–6.78 (1H, m), 3.86–3.82 (1 H), 3.64 (4H, d, J=4.9 Hz), 2.58 (2H, q, J=15.1, 7.6 Hz), 1.19 (3H, t, J=7.6 Hz); 19F-NMR (376 MHz; CD3OD) 8–132.4, −134.6, −147.2; MS(APCI+)=385; Anal.calcd/found for C18H19F3N2O4: C, 56.25/56.38; H, 4.98/4.81; N, 7.29/7.25.

Workup

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

Sources & evidence

ORD record
ord-a7104acbbd12461a8b874be5fbda6497
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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