Hydrochloric Acid → HCID 57948952, compound

HRID 1992271Notes

Reaction equation

HRID 1992271 reaction equation
C([NH:9][C:10]([NH:12][C@@:13]([C:18]1[CH:23]=[C:22]([Br:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])([CH3:17])[CH2:14][CH2:15]O)=[S:11])(=O)C1C=CC=CC=1.Cl.[OH-].[Na+]>O1CCOCC1>[Br:24][C:22]1[C:21]([F:25])=[CH:20][C:19]([F:26])=[C:18]([C@:13]2([CH3:17])[CH2:14][CH2:15][S:11][C:10]([NH2:9])=[N:12]2)[CH:23]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 57948924HCID 57948924, compound

Product 1

HCID 57948952HCID 57948952, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-1-benzoyl-3-[1-(5-bromo-2,4-difluoro-phenyl)-3-hydroxy-1-methyl-propyl]-thiourea (41 g, 68 mmoles) in 1,4-dioxane (20 mL) is added an aqueous solution of HCl (5 N, 407 mL, 2.0 moles, 30 equiv). The resulting suspension is warmed to 100° C. After stirring for 20 h, the reaction is concentrated under reduced pressure. The resulting mixture is treated with an aqueous solution of HCl (5 N, 407 mL, 2.0 moles) and stirred at 100° C. for 18 h. The suspension is cooled to 10° C. and the pH is adjusted to pH 10 with a 50% aqueous solution of NaOH. The resulting aqueous solution is extracted with ethyl acetate. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel flash column chromatography eluting with a step gradient of hexane:acetone (4:1) to hexane:acetone (3:1) to give the title compound (57% yield, 85% purity as determined by LCMS): MS (m/z): 321, 323 (M+1).

Workup

  1. concentrationthe reaction is concentrated under reduced pressure
  2. stirringstirred at 100° C. for 18 h
  3. temperatureThe suspension is cooled to 10° C.
  4. extractionThe resulting aqueous solution is extracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by silica gel flash column chromatography
  9. washeluting with a step gradient of hexane:acetone (4:1) to hexane:acetone (3:1)

Sources & evidence

ORD record
ord-c165cf57d65b43f79b095d0a8a7bf099
Source dataset
uspto-grants-2010_01
Patent number
US07648983B2

Reaction notes

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