Acetic Acid → HCID 10126237, compound

HRID 2181442Notes

Reaction equation

HRID 2181442 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][Si](C)(C)C)[CH:5]=[CH:4][C:3]=1[NH:14][C:15]1[C:27]([F:28])=[C:26]([F:29])[CH:25]=[CH:24][C:16]=1[C:17]([NH:19][O:20][CH2:21][CH2:22][OH:23])=[O:18].C(O)(=O)C.[F-].[Cs+]>CO>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[CH:9])[CH:5]=[CH:4][C:3]=1[NH:14][C:15]1[C:27]([F:28])=[C:26]([F:29])[CH:25]=[CH:24][C:16]=1[C:17]([NH:19][O:20][CH2:21][CH2:22][OH:23])=[O:18]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 25953Cesium fluorideHCID 12135110HCID 12135110, compound2×

Product 1

HCID 10126237HCID 10126237, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product of Example 8, Step A, 2-(2-Chloro-4-trimethylsilanylethynyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (0.704 g, 1.60 mmol) in methanol (21 mL) was added acetic acid (0.1 mL) and cesium fluoride (0.600 g, 3.95 mmol). The resultant solution was stirred at ambient temperature. After 26 hours, the reaction mixture was partitioned between ethyl acetate (100 mL) and water (25 mL) and the organic layer was further washed with water (25 mL) and saturated brine (25 mL). The combined aqueous was extracted with ethyl acetate (50 mL). The combined organics were dried over magnesium sulfate and concentrated to a dark brown oil. Ether (15 mL) was added and crystallization ensued. The cream-colored solid was collected and dried under vacuum at 70° C. to afford 2-(2-chloro-4-ethynyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (0.290 g): m.p. 155-157° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.94 (br s, 1 H), 8.95 (br s, 1 H), 7.55 (d, J=2.0 Hz, 1 H), 7,48 (m, 1 H), 7.34-7.27 (m, 2 H), 6.74 (dd, J=8.4, 6.5 Hz, 1 H), 4.71 (br s, 1 H), 4.13 (s, 1 H), 3.88 (t, J=4.6 Hz, 2 H), 3.58 (t, J=4.7 Hz, 2H); MS (APCI+)=367.0; MS (APCI−)=365.0; Anal. Calcd/found for C17H13ClF2N2O3: C, 55.67/55.54; H, 3.57/3.23; N, 7.64/7.31. Concentration of the mother liquor afforded an additional crop of product (0.209 g, 85% total yield).

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate (100 mL) and water (25 mL)
  2. washthe organic layer was further washed with water (25 mL) and saturated brine (25 mL)
  3. extractionThe combined aqueous was extracted with ethyl acetate (50 mL)
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. concentrationconcentrated to a dark brown oil
  6. additionEther (15 mL) was added
  7. customcrystallization
  8. customThe cream-colored solid was collected
  9. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-289f6882a9c84a8baebe0f2189eefd96
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

Loading…