1,2-Dichloroethane → tert-butyl 1-((S)-2-carbamoylpyrrolidin-1-yl)-5-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-1,5-dioxopentan-2-ylcarbamate

HRID 910405Notes

Reaction equation

HRID 910405 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][CH2:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[CH2:22][O:23][CH3:24])=[O:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:25]1[CH2:32][CH2:31][CH2:30][C@H:26]1[C:27]([NH2:29])=[O:28].C1C=C2N=NN(O)C2=CC=1.O.C(Cl)CCl>C(Cl)Cl>[C:27]([C@@H:26]1[CH2:30][CH2:31][CH2:32][N:25]1[C:10](=[O:12])[CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:13][CH2:14][C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[CH2:22][O:23][CH3:24])=[O:16])(=[O:28])[NH2:29]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 111306L-ProlinamideHCID 27960291-Hydroxybenzotriazole hydrateHCID 673932042-tert-butoxycarbonylamino-5-((S)-2-methoxymethyl-pyrrolidin-1-yl)-5-oxo-pentanoic acid

Product 1

HCID 67392667tert-butyl 1-((S)-2-carbamoylpyrrolidin-1-yl)-5-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-1,5-dioxopentan-2-ylcarbamateYield 81.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 2-tert-butoxycarbonylamino-5-((S)-2-methoxymethyl-pyrrolidin-1-yl)-5-oxo-pentanoic acid (0.34 g, 1 mmol), L-prolinamide (0.11 g, 1 mmol), and HOBt hydrate (0.14 g, 1 mmol) in CH2Cl2 (5 mL) was added EDC (0.19 g, 1 mmol). The reaction mixture was stirred at ambient temperature for 12 h, diluted with CH2Cl2 (20 mL), washed sequentially with saturated aqueous sodium bicarbonate (10 mL), 0.5 N aqueous citric acid (10 mL) and brine (10 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a crude a viscous oil. The crude oil was purified by flash chromatography (silica gel, 2 to 8% CH3OH/CH2Cl2 gradient) to give the title compound (0.36 g, 81%) as a foamy solid.

Workup

  1. washwashed sequentially with saturated aqueous sodium bicarbonate (10 mL), 0.5 N aqueous citric acid (10 mL) and brine (10 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto yield a crude a viscous oil
  6. customThe crude oil was purified by flash chromatography (silica gel, 2 to 8% CH3OH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-380699cdf4ab480f91b33115255d3aad
Source dataset
uspto-grants-2011_09
Patent number
US08022096B2

Reaction notes

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