Hydrochloric Acid → 4-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 79064Notes

Reaction equation

HRID 79064 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[CH:12][C:13]2[S:17][N:16]=[CH:15][C:14]=2[C:18]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=1[F:27])=[O:9])=C.Cl>CO>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[CH:12][C:13]2[S:17][N:16]=[CH:15][C:14]=2[C:18]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=1[F:27])=[O:9]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86656247HCID 86656247, compound

Product 1

HCID 446031464-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid (2-hydroxy-ethoxy)-amideYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 4-(2-fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide (258 mg, 0.52 mmol) in methanol (10 mL) was added hydrochloric acid (1.0 mL, 1M solution, 1.0 mmol) and the reaction mixture stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was separated and washed with water then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—SPE, gradient 0-100% ethyl acetate in cyclohexane) to give the title compound as a white solid (140 mg, 57%). LCMS (Method A): RT=9.72 min, [M+H]+=474. 1H NMR (CD3OD, 400 MHz) 8.57 (1H, s), 7.71 (1H, d, J=8.53 Hz), 7.69-7.61 (1H, m), 7.51 (1H, dd, J=10.43, 1.94 Hz), 7.33 (1H, d, J=8.54 Hz), 6.67 (1H, t, J=8.63 Hz), 3.92 (2H, t, J=4.60 Hz), 3.70 (2H, t, J=4.60 Hz).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between ethyl acetate and saturated aqueous NaHCO3
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialbrine, dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-61f7a9230a82426c88ff683c91f83fb5
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

Loading…