4-Methylmorpholine → HCID 86616815, compound

HRID 639128Notes

Reaction equation

HRID 639128 reaction equation
[C:1]([C@H:3]1[CH2:7][N:6]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][C@H:4]1[C:15]([OH:17])=O)#[N:2].C[N:19]1CCOCC1.ClC(OCC(C)C)=O>C1COCC1>[C:1]([C@@H:3]1[CH2:7][N:6]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][C@@H:4]1[C:15]([NH2:19])=[O:17])#[N:2]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 59026164HCID 59026164, compound

Product 1

HCID 86616815HCID 86616815, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

Crude (3S,4R)-4-cyano-1-(phenylmethyl)-3-pyrrolidinecarboxylic acid (3.24 g) was dissolved in THF (50 mL). N-methyl morpholine (0.93 mL, 8.49 mmol) was added and the solution allowed to stir overnight. A bit of solid remains undissolved. The solution was cooled to −15 degrees C. in an ethylene glycol/dry ice bath. Isobutyl chloroformate (1.1 mL, 8.49 mL) was added and the reaction stirred at −15 degrees C. for 1 hour. Ammonia was then bubbled through the solution for 20 minutes. The solution was allowed to warm to ambient temperature and the solvent removed under reduced pressure. The crude material was chromatographed on silica gel to yield a solid (1.56 g, 88% over 2 steps). LCMS: m/z 230.4 (MH+).

Workup

  1. stirringthe reaction stirred at −15 degrees C
  2. waitfor 1 hour
  3. customAmmonia was then bubbled through the solution for 20 minutes
  4. temperatureto warm to ambient temperature
  5. customthe solvent removed under reduced pressure
  6. customThe crude material was chromatographed on silica gel
  7. customto yield a solid (1.56 g, 88% over 2 steps)

Sources & evidence

ORD record
ord-1a4e4dceed6543cfb1148b5e38610d9d
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

Loading…