Hydrochloric Acid → 3-Chloro-N-{4-[2-(2-hydroxy-3-oxo-4-morpholinyl)ethyl]-1,3-thiazol-2-yl}-2-methylbenzenesulfonamide

HRID 1435699Notes

Reaction equation

HRID 1435699 reaction equation
ClC(Cl)C(Cl)=[O:4].Cl[CH:8](Cl)[C:9]([N:11]([CH2:15][CH2:16][C:17]1[N:18]=[C:19]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=2[CH3:33])(=[O:25])=[O:24])[S:20][CH:21]=1)[CH2:12][CH2:13][OH:14])=[O:10].[OH-].[K+].Cl>C(OCC)(=O)C.C(=O)([O-])[O-].[Na+].[Na+].C1COCC1.O>[Cl:32][C:28]1[C:27]([CH3:33])=[C:26]([S:23]([NH:22][C:19]2[S:20][CH:21]=[C:17]([CH2:16][CH2:15][N:11]3[CH2:12][CH2:13][O:14][CH:8]([OH:4])[C:9]3=[O:10])[N:18]=2)(=[O:25])=[O:24])[CH:31]=[CH:30][CH:29]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 6593Dichloroacetyl chlorideHCID 14797Potassium HydroxideHCID 865949592,2-Dichloro-N-[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]-N-(2-hydroxyethyl)acetamide

Product 1

HCID 112474673-Chloro-N-{4-[2-(2-hydroxy-3-oxo-4-morpholinyl)ethyl]-1,3-thiazol-2-yl}-2-methylbenzenesulfonamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

To a slurry of EXAMPLE 208A (0.759 g, 2.02 mmol) in ethyl acetate (6 mL) and saturated sodium carbonate (6 mL) at 0° C., 2,2-dichloroacetic acid chloride was added neat in portions (15×40 μl 3 eq.). The mixture was stirred for 1.5 h at room temperature. The reaction mixture was then extracted with ethyl acetate (3×40 mL), washed with brine (40 mL), and dried over magnesium sulfate. The solvent was evaporated and 1.10 g of crude N-acetylated product was isolated as yellow oil (70% pure by HPLC). The crude 2,2-Dichloro-N-[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]-N-(2-hydroxyethyl)acetamide (1.00 g, 2.05 mmol) was dissolved in THF (27 mL) and water (27 mL). The solution was cooled to 0° C. and the pH was adjusted to 14-15 with aqueous KOH (50%). After 20 h, the reaction mixture was neutralized with aqueous HCl (1 M, 12 mL). The reaction mixture was extracted with ethyl acetate (3×25 mL), and the combined organic phases was dried over magnesium sulfate. Removal of solvent and purification by silica gel chromatography (gradient of 2-4% methanol in DCM) gave the title compound as a white solid (20 mg): HRMS calcd (found) for C16H18ClN3O5S2 m/z 431.0376 (431.0380).

Workup

  1. customat 0° C.
  2. extractionThe reaction mixture was then extracted with ethyl acetate (3×40 mL)
  3. washwashed with brine (40 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was evaporated
  6. custom1.10 g of crude N-acetylated product was isolated as yellow oil (70% pure by HPLC)
  7. temperatureThe solution was cooled to 0° C.
  8. waitAfter 20 h
  9. extractionThe reaction mixture was extracted with ethyl acetate (3×25 mL)
  10. dry with materialthe combined organic phases was dried over magnesium sulfate
  11. customRemoval of solvent and purification by silica gel chromatography (gradient of 2-4% methanol in DCM)

Sources & evidence

ORD record
ord-bd26caf2ab2448b5a022200a49e44e05
Source dataset
uspto-grants-2009_11
Patent number
US07618961B2

Reaction notes

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