4-Methylmorpholine → Boc-prolylproline benzyl ester

HRID 1720499Notes

Reaction equation

HRID 1720499 reaction equation
Cl.[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CN1CCOCC1.[C:24]([O:28][C:29]([N:31]1[CH2:38][CH2:37][CH2:36][C@H:32]1[C:33](O)=[O:34])=[O:30])([CH3:27])([CH3:26])[CH3:25].C1C=CC2N(O)N=NC=2C=1>ClCCl.C(OCC)(=O)C.O>[CH2:2]([O:9][C:10](=[O:16])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:33](=[O:34])[C@@H:32]1[CH2:36][CH2:37][CH2:38][N:31]1[C:29]([O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:30])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 13091041Boc-prolylproline benzyl esterYield 89.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of L-proline benzyl ester hydrochloride (3.37 g) in dichloromethane (60 ml) were added N-methylmorpholine (1.54 ml), N-(t-butoxycarbonyl)-L-proline (3.00 g), HOBt (2.08 g) and water-soluble carbodiimide hydrochloride (2.95 g) in order, followed by stirring for 1 hour. After stirring at room temperature for 17 hours, the reaction mixture was poured into ethyl acetate, washed with 1N hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and saturated brine in order, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluate; hexane-ethyl acetate) to give 5.00 g of the title compound.

Workup

  1. stirringAfter stirring at room temperature for 17 hours
  2. washwashed with 1N hydrochloric acid
  3. dry with materiala saturated aqueous solution of sodium bicarbonate and saturated brine in order, dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (eluate; hexane-ethyl acetate)

Sources & evidence

ORD record
ord-6962b7aed74d4ce884e0671dfbddb155
Source dataset
uspto-grants-1996_04
Patent number
US05506256

Reaction notes

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