Dimethylamine → N,N-dimethyl-2-pyrrolidin-3-yl-acetamide

HRID 2234660Notes

Reaction equation

HRID 2234660 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([CH2:13][C:14](=[O:18])[N:15]([CH3:17])[CH3:16])[CH2:9]1)=O)(C)(C)C.ClC1N=C(Cl)N=C(OC)N=1.CN1CCOCC1.CNC.FC(F)(F)C(O)=O>O1CCCC1.ClCCl.O>[CH3:17][N:15]([CH3:16])[C:14](=[O:18])[CH2:13][CH:10]1[CH2:11][CH2:12][NH:8][CH2:9]1

Participants

9

Reactant 5

HCID 674DimethylamineHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 192672,4-Dichloro-6-methoxy-3,5-triazineHCID 686918623-Dimethylcarbamoylmethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57731570N,N-dimethyl-2-pyrrolidin-3-yl-acetamideYield 77.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-dimethylcarbamoylmethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.36 mmol) in tetrahydrofuran (20 ml) was added 2,4-dichloro-6-methoxy-[1,3,5]triazine (765 mg, 4.36 mmol) and N-methyl morpholine (1.44 ml, 13 mmol). The mixture was stirred at room temperature for 1 hour. A dimethylamine solution in tetrahydrofuran (11 ml, 2.0 M, 21.3 mmol) was added in one portion. The mixture was stirred at room temperature for 15 hours. Water (2.0 mL) was added, and the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate (20 mL) and aqueous 1 N hydrochloric acid (15 ml). The organic layer was washed with sodium bicarbonate (sat. 10 ml) and brine (10 mL), then dried over sodium sulfate and evaporated in vacuo to give the crude product (990 mg, 88%). The crude material was dissolved in dichloromethane (2.0 mL) and trifluoroacetic acid (2.0 ml) was added. The mixture was stirred at room temperature for 90 minutes. It Was then concentrated in vacuo and the residue partitioned between saturated aqueous sodium bicarbonate (10 mL) and chloroform. The aqueous layer was extracted three times with chloroform (15 ml) and the combined organic layers were dried over sodium sulfate and concentrated in vacuo to give 530 mg (77% over 2 steps) of N,N-dimethyl-2-pyrrolidin-3-yl-acetamide as a yellowish oil, which was used in the subsequent step without further purification.

Workup

  1. stirringThe mixture was stirred at room temperature for 15 hours
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate (20 mL) and aqueous 1 N hydrochloric acid (15 ml)
  4. washThe organic layer was washed with sodium bicarbonate (sat. 10 ml) and brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. customevaporated in vacuo
  7. customto give the crude product (990 mg, 88%)
  8. stirringThe mixture was stirred at room temperature for 90 minutes
  9. concentrationIt Was then concentrated in vacuo
  10. customthe residue partitioned between saturated aqueous sodium bicarbonate (10 mL) and chloroform
  11. extractionThe aqueous layer was extracted three times with chloroform (15 ml)
  12. dry with materialthe combined organic layers were dried over sodium sulfate
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c1e6f704e85646da89722aba69bad529
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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