4-Methylmorpholine → (2S)-1-[N-(tert-Butoxycarbonyl)-L-prolyl]-2-(1-hydroxy-2-phenoxyethyl)pyrrolidine

HRID 1720529Notes

Reaction equation

HRID 1720529 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]([OH:22])[CH2:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7])(C)(C)C.[C:23]([O:27][C:28]([N:30]1[CH2:37][CH2:36][CH2:35][C@H:31]1C(O)=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>Cl.O1CCOCC1.CN(C=O)C>[C:23]([O:27][C:28]([N:30]1[CH2:37][CH2:36][CH2:35][C@H:31]1[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]([OH:22])[CH2:14][O:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:7])=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 57278887(2S)-1-(t-butoxycarbonyl)-2-(1-hydroxy-2-phenoxyethyl)-pyrrolidine

Product 1

HCID 70050944(2S)-1-[N-(tert-Butoxycarbonyl)-L-prolyl]-2-(1-hydroxy-2-phenoxyethyl)pyrrolidineYield 82.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 204431481,4-Dioxane hydrochlorideSolvent

Conditions

Temperature
-25 °C

Procedure

(2S)-1-(tert-Butoxycarbonyl)-2-(1-hydroxy-2-phenoxyethyl)-pyrrolidine (1.93 g) was dissolved in 31 ml of 4N hydrochloric acid/1,4-dioxane, and the mixture was,stirred at room temperature for 0.5 hour. The reaction mixture was concentrated to dryness, and the residue obtained was dissolved in DMF (15 ml), after which N-(tert-butoxycarbonyl)-L-proline (1.36 g), N-methylmorpholine (0.69 ml), and HOBt (1.02g) were added thereto. After the reaction mixture was cooled to -25° C., DCC (1.30 g) was added thereto, and the mixture was stirred at -25° C. to 0° C. for 3 hours, and then at room temperature for 16 hours. The precipitated dicyclohexylurea was filtered off, and the filtrate was concentrated. The residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate, and saturated brine successively, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluate: chloroform-methanol) to give 2.10 g of the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue obtained
  3. waitat room temperature for 16 hours
  4. filtrationThe precipitated dicyclohexylurea was filtered off
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. washwashed with saturated aqueous sodium bicarbonate, and saturated brine successively
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography (eluate: chloroform-methanol)

Sources & evidence

ORD record
ord-b526a1e60300499b9abbabac196c6755
Source dataset
uspto-grants-1996_04
Patent number
US05506256

Reaction notes

Loading…