Acetyl chloride → HCID 10112859, compound

HRID 1766250Notes

Reaction equation

HRID 1766250 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)=[CH:8][C:7]([OH:18])=[CH:6][CH:5]=2.[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:21]=1[S:27](Cl)(=[O:29])=[O:28].C(Cl)(=O)C>C1COCC1.[OH-].[Na+].O.C(O)C>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)=[CH:8][C:7]([O:18][S:27]([C:21]1[C:22]([F:26])=[CH:23][CH:24]=[CH:25][C:20]=1[F:19])(=[O:29])=[O:28])=[CH:6][CH:5]=2

Participants

8

Reactant 3

HCID 6367Acetyl chlorideHCID 27342712,6-Difluorobenzenesulfonyl chlorideHCID 17980111HCID 17980111, compound

Product 1

HCID 10112859HCID 10112859, compoundYield 65.8%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 2-methyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-1H-indole (4.05 mmol, 0.989 g) in THF (12 mL) and 1M sodium hydroxide (4.09 mL) was treated with 2,6-difluorobenzenesulfonyl chloride (4.46 mmol, 0.948 g). After stirring one hour at room temperature the reaction was diluted with water (25 mL) and extracted with ethyl acetate (3×25 mL). The organic phases were combined, concentrated in vacuo to afford foam. The free amine was converted to the hydrochloride salt. Acetyl chloride (approximately 1.2 eq) was added to a cooled solution of ethanol (0° C.). After stirring approximately five minutes, this solution was added to a solution of the free amine in ethanol. The biphasic solution was concentrated in vacuo to foam. The foam was dissolved in acetone, crystals formed, collected by filtration to afford 1.12 g (60%) of the title compound: mp=138° C. (decomposes); mass spectrum (ion spray): m/z=420 (M−1); Calculated for C21H22F2N2O3S-HCl-0.2H20-0.6C3H6O: C, 55.28; H, 5.49; N, 5.66. Found: C, 55.42; H, 5.46; N, 5.30

Workup

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. concentrationconcentrated in vacuo
  3. customto afford foam
  4. stirringAfter stirring approximately five minutes
  5. concentrationThe biphasic solution was concentrated in vacuo to foam
  6. dissolutionThe foam was dissolved in acetone
  7. customcrystals formed
  8. filtrationcollected by filtration

Sources & evidence

ORD record
ord-7338568a009d476ab1f69bd872b532b7
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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