Methylamine → 5-(4-Chloro-3-chlorosulfonylphenyl)-5-hydroxy-1-methyl-2-pyrrolidone

HRID 225169Notes

Reaction equation

HRID 225169 reaction equation
[CH2:1]([N:3](CC)CC)C.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:21])[CH2:16][CH2:17][C:18](O)=[O:19])=[CH:11][C:10]=1[S:22]([Cl:25])(=[O:24])=[O:23].ClC(OCC)=O.CN>O1CCCC1.O>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([OH:21])[N:3]([CH3:1])[C:18](=[O:19])[CH2:17][CH2:16]2)=[CH:11][C:10]=1[S:22]([Cl:25])(=[O:24])=[O:23]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 233291684-(4-Chloro-3-chlorosulfonylphenyl)-4-oxobutanoic acid

Product 1

HCID 142568045-(4-Chloro-3-chlorosulfonylphenyl)-5-hydroxy-1-methyl-2-pyrrolidone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2.1 g of triethylamine are rapidly added dropwise to a mixture of 6.2 g 4-(4-chloro-3-chlorosulfonylphenyl)-4-oxobutanoic acid and 2.2 g of ethyl chloroformate in 20 ml of absolute tetrahydrofurane at a rate such that the internal temperature is maintained between -5° and -10° C. The mixture is stirred for about 5 to 10 minutes at -5° to 0° C. and 1.55 ml of a 4% strength solution of gaseous methylamine in tetrahydrofurane is rapidly added dropwise. Stirring is continued for 15 to 20 minutes at 10°-15° C., the reaction mixture is poured into water and extracted twice, each time with 80 ml of ethyl acetate. The organic phase is washed once with 50 ml of 0.01 N hydrochloric acid at 0° C. and once with cold bicarbonate solution, dried for one hour over Na2SO4 at 0°-10° C. while stirring with a magnetic stirrer and concentrated on a rotavapor (bath temperature ≤30° C.). The 5-(4-chloro-3-chlorosulfonylphenyl)-5-hydroxy-1-methyl-2-oxo-pyrrolidine is mostly obtained in the form of an amorphous residue. After addition of 20 ml of 40% strength aqueous methylamine solution (cooling) the mixture is stirred overnight at room temperature, concentrated and allowed to crystallize under water. Colorless crystals, melting point 112°-114° C. (from ethanol).

Workup

  1. temperatureis maintained between -5° and -10° C
  2. stirringStirring
  3. waitis continued for 15 to 20 minutes at 10°-15° C.
  4. extractionextracted twice
  5. washThe organic phase is washed once with 50 ml of 0.01 N hydrochloric acid at 0° C. and once with cold bicarbonate solution
  6. dry with materialdried for one hour over Na2SO4 at 0°-10° C.
  7. stirringwhile stirring with a magnetic stirrer
  8. concentrationconcentrated on a rotavapor (bath temperature ≤30° C.)

Sources & evidence

ORD record
ord-8ec5ba3fcc90437bba8529c361c6afdd
Source dataset
uspto-grants-1980_11
Patent number
US04235918

Reaction notes

Loading…