4-Methylmorpholine → HCID 59401911, compound

HRID 1516539Notes

Reaction equation

HRID 1516539 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][C@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1.CN1CCOCC1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CO>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C:13]([N:18]2[CH2:19][CH2:20][CH2:21][C@@H:17]2[CH3:16])=[O:15])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1512492(3S)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6999702(2S)-2-methylpyrrolidine

Product 1

HCID 59401911HCID 59401911, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

(3S)-Pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (purchased from Astatech, Inc, 0.5 g, 2.3 mmol) was dissolved in DCM (20 mL) and the solution was cooled to an ice-water bath. To this solution was added a solution of (S)-2-methyl-pyrrolidine (purchased from Advanced Asymmetric, Inc., 235 mg, 2.76 mmol, 1.2 equiv.) in 1 mL of DCM, followed by N-methylmorpholine (700 mg, 6.9 mmol, 3 equiv.) and 1-hydroxylbenzotriazole (HOBT) (404 mg, 3 mmol, 1.3 equiv.) sequentially, and finally EDC.HCl (576 mg, 3 mmol, 1.3 equiv.). The resultant clear light brown solution was stirred at r.t. overnight. TLC (10% MeOH in DCM) and LC/MS detected the product peak at a retention time of 3.238 min with MS 227 (M-t-Bu). The reaction was quenched with aqueous saturated sodium bicarbonate solution (10 mL) and 10 mL of DCM. The two layers were separated, and the aqueous layer was extracted with DCM (15 mL×2). The combined DCM extracts were washed successively with sodium bicarbonate (10 mL) and brine (10 mL), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuum to obtain the title compound, 0.65 g (100% yield), as a thick oil.

Workup

  1. temperaturethe solution was cooled to an ice-water bath
  2. customThe reaction was quenched with aqueous saturated sodium bicarbonate solution (10 mL) and 10 mL of DCM
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with DCM (15 mL×2)
  5. washThe combined DCM extracts were washed successively with sodium bicarbonate (10 mL) and brine (10 mL)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-9d89bdb8ca054c65b53d7007cb24236a
Source dataset
uspto-grants-2012_07
Patent number
US08227504B2

Reaction notes

Loading…