Dimethylamine → N,N-dimethylpyrrolidine-3-carboxamide

HRID 2234662Notes

Reaction equation

HRID 2234662 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9]1)=O)(C)(C)C.Cl[C:17]1N=C(Cl)N=[C:19](OC)[N:18]=1.CN1CCOCC1.CNC.FC(F)(F)C(O)=O>O1CCCC1.ClCCl.O>[CH3:17][N:18]([CH3:19])[C:13]([CH:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)=[O:15]

Participants

9

Reactant 5

HCID 674DimethylamineHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 192672,4-Dichloro-6-methoxy-3,5-triazineHCID 27605291-((Tert-butoxy)carbonyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 23090229N,N-dimethylpyrrolidine-3-carboxamideYield 27.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (980 mg, 4.55 mmol) in tetrahydrofuran (20 ml) was added 2,4-dichloro-6-methoxy-[1,3,5]triazine (800 mg, 4.55 mmol) and N-methyl morpholine (1.0 ml, 0.91 mmol). The mixture was stirred at room temperature for 1 hour. Dimethylamine (2.0 M in tetrahydrofuran, 11 ml, 22.0 mmol) was added in one portion. The mixture was stirred at room temperature for an additional 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 1 N hydrochloric acid (15 ml). The organic layer was washed with a saturated aqueous solution of sodium bicarbonate (10 ml) and brine (10 ml), then dried over sodium sulfate, filtered, and concentrated in vacuo to give the crude product (260 mg, 20%). The crude material was dissolved in dichloromethane (1.0 ml) and trifluoroacetic acid (1.0 ml) was added. The mixture was stirred at room temperature for 90 minutes, and then concentrated in vacuo. The residue was taken into saturated aqueous sodium bicarbonate (10 ml) and extracted three times with chloroform (10 ml). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give 180 mg (20% over 2 steps) of pyrrolidine-3-carboxylic acid dimethylamide.

Workup

  1. stirringThe mixture was stirred at room temperature for an additional 15 hours
  2. concentrationthe mixture was concentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate (20 ml) and 1 N hydrochloric acid (15 ml)
  4. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate (10 ml) and brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product (260 mg, 20%)
  9. stirringThe mixture was stirred at room temperature for 90 minutes
  10. concentrationconcentrated in vacuo
  11. extractionextracted three times with chloroform (10 ml)
  12. dry with materialThe combined organic layers were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0d5136ab084f45d0ad50253cd6a518ad
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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