4-Methylmorpholine → (2S)-1-(phenylmethyl)-2-(1-pyrrolidinylcarbonyl)pyrrolidine

HRID 1366642Notes

Reaction equation

HRID 1366642 reaction equation
Cl.[C:2]1([CH2:8][N:9]2[CH2:16][CH2:15][CH2:14][C@H:10]2[C:11]([OH:13])=O)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:17]1[CH:18]=CC2N(O)N=[N:23][C:21]=2[CH:22]=1.CN1CCOCC1.N1CCCC1.CCN=C=NCCCN(C)C>C(Cl)Cl>[C:2]1([CH2:8][N:9]2[CH2:16][CH2:15][CH2:14][C@H:10]2[C:11]([N:23]2[CH2:18][CH2:17][CH2:22][CH2:21]2)=[O:13])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 573677341-Benzyl-L-proline hydrochloride

Product 1

HCID 66936490(2S)-1-(phenylmethyl)-2-(1-pyrrolidinylcarbonyl)pyrrolidineYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(Phenylmethyl)-L-proline hydrochloride (2.0 g, 8.247 mmol) and HOBt (1.34 g, 9.928 mmol) were dissolved in CH2Cl2 (50 mL), and 4-methylmorpholine (3.63 mL, 33.09 mmol), pyrrolidine (0.760 mL, 9.101 mmol), and EDCI (1.906 g, 9.928 mmol) were added. The solution was stirred overnight, and was then washed with water (50 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL), and the combined organic layers were dried over anhydrous MgSO4 and concentrated in vacuo. This crude product was purified by flash chromatography (Combiflash, 0-100% ethyl acetate/hexanes, 1% triethylamine) to provide (2S)-1-(phenylmethyl)-2-(1-pyrrolidinylcarbonyl)pyrrolidine (1.619 g, 76%). LCMS: (M+H)+: 259.2

Workup

  1. washwas then washed with water (50 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×50 mL)
  3. dry with materialthe combined organic layers were dried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. customThis crude product was purified by flash chromatography (Combiflash, 0-100% ethyl acetate/hexanes, 1% triethylamine)

Sources & evidence

ORD record
ord-081cd6fe832148078b1f743da49bfc2b
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

Loading…