4-Methylmorpholine → HCID 58226718, compound

HRID 1411431Notes

Reaction equation

HRID 1411431 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:18]1CCOCC1.ClC(OCC(C)C)=O>O1CCCC1>[C:14]([C@@H:9]1[CH2:10][C:11](=[CH2:13])[CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])(=[O:16])[NH2:18]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 21727417(2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acid

Product 1

HCID 58226718HCID 58226718, compoundYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

(S)-1-(tert-Butoxycarbonyl)-4-methylenepyrrolidine-2-carboxylic acid (1.05 g, 4.48 mmol) and N-methylmorpholine (0.64 mL, 5.83 mmol) were dissolved in tetrahydrofuran (25 mL) and cooled to −15° C. in a dry ice/acetone bath. Isobutyl chloroformate (0.65 mL, 4.93 mmol) was added dropwise and the solution was stirred for 15 minutes. The internal temperature was lowered to −25° C. and ammonia (g) was bubbled through the solution for 2 minutes, then the flask was transferred to an ice bath and stirred for another 20 minutes. The solution was poured into brine and extracted into ethyl acetate, dried over magnesium sulfate, filtered and concentrated. This residue was triturated with ether/hexanes, filtered, and dried to give 0.97 g (81%) of (S)-tert-butyl 2-carbamoyl-4-methylenepyrrolidine-1-carboxylate as a white solid.

Workup

  1. customwas lowered to −25° C.
  2. customammonia (g) was bubbled through the solution for 2 minutes
  3. customthe flask was transferred to an ice bath
  4. stirringstirred for another 20 minutes
  5. additionThe solution was poured into brine
  6. extractionextracted into ethyl acetate
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThis residue was triturated with ether/hexanes
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-7c8a35457c7a415eb22b061028dc12b9
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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