Chloroacetone → HCID 20266384, compound

HRID 1719708Notes

Reaction equation

HRID 1719708 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[OH-].[K+].[Li]CCCC.[Cl:16][CH2:17][C:18](=[O:20])[CH3:19]>CCOCC.CCCCCC.C(O)(=O)C>[N:6]1[CH:7]=[CH:8][C:3]([C:18]([OH:20])([CH3:19])[CH2:17][Cl:16])=[CH:4][CH:5]=1

Participants

8

Reactant 4

HCID 6571ChloroacetoneHCID 14797Potassium HydroxideHCID 881004-Bromopyridinium chlorideHCID 178418339Butyllithium

Product 1

HCID 20266384HCID 20266384, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Procedure

A mixture of 4-bromopyridine hydrochloride (3.8 g) and potassium hydroxide (1.1 g) was stirred at room temperature in anhydrous ether (20 cm3) for 0.5 hours. The mixture was then cooled -70°, n-BuLi (12.2 cm3 of a 1.6M solution in hexane) was added, the mixture was stirred for 1 hour and chloroacetone (1.39 g) in ether (10 cm3) was added. Stirring was continued for 1 hour, acetic acid (1.2 g) was added and the mixture was partitioned between sodium carbonate solution and ether. The organic phase was dried (MgSO4) and evaporated and the residue was chromatographed on silica ("Merck" 60.9385) eluting with ethyl acetate:petrol (b.p. 60°-80°), 2:3, to give 2-(4-pyridyl)-2-hydroxypropylchloride as a waxy solid (0.6 g). This material was taken without further purification into DMF (5 cm3) and this was then added to a solution of 2-sodioisothiazolidine-1,1 -dioxide [made from isothiazolidine-1,1-dioxide (0.65 g) and sodium hydride (0.5 g of a 50% dispersion in oil) in DMF (10 cm3)] and the mixture was heated for 3 hours at 130°. Volatile material was removed in vacuo, the residue was partitioned between chloroform and water, the aqueous phase was extracted further with chloroform (2×25 cm3) and the combined extracts were dried (MgSO4) and evaporated to afford an oil. Chromatography on silica ("Merck" 60.9385) eluting with methanol:chloroform, 1:19, gave 2-[2-(4-pyridyl)-2-hydroxy]prop-1-ylisothiazolidine-1,1-dioxide as an oil (0.48 g) which was used without further purification.

Workup

  1. temperatureThe mixture was then cooled -70°
  2. stirringStirring
  3. waitwas continued for 1 hour
  4. customthe mixture was partitioned between sodium carbonate solution and ether
  5. dry with materialThe organic phase was dried (MgSO4)
  6. customevaporated
  7. customthe residue was chromatographed on silica ("Merck" 60.9385)
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-f5b6f66ba88948ed8887481ca283ea27
Source dataset
uspto-grants-1985_09
Patent number
US04542132

Reaction notes

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