1,2-Dichloroethane → 2-tert-butoxycarbonylamino-5-((S)-2-methoxymethyl-pyrrolidin-1-yl)-5-oxo-pentanoic acid methyl ester

HRID 910403Notes

Reaction equation

HRID 910403 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:15]([O:17][CH3:18])=[O:16])[CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:19][O:20][CH2:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][NH:23]1.O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>C(Cl)Cl>[CH3:18][O:17][C:15](=[O:16])[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][CH2:11][C:12]([N:23]1[CH2:24][CH2:25][CH2:26][C@H:22]1[CH2:21][O:20][CH3:19])=[O:14]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 671217(S)-(+)-2-(Methoxymethyl)pyrrolidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 139430724-((tert-Butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid

Product 1

HCID 673924162-tert-butoxycarbonylamino-5-((S)-2-methoxymethyl-pyrrolidin-1-yl)-5-oxo-pentanoic acid methyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-(tert-butoxycarbonylamino)-5-methoxy-5-oxopentanoic acid (1.05 g, 4 mmol), (S)-2-(methoxymethyl)-pyrrolidine (0.46 g, 4 mmol), and 1-hydroxybenzotriazole hydrate (HOBt hydrate, 0.54 g, 4 mmol) in CH2Cl2 (10 mL) was added EDC (0.77 g, 4 mmol). The reaction mixture was stirred at ambient temperature for 12 h, diluted with CH2Cl2 (40 mL), washed sequentially with saturated aqueous sodium bicarbonate (20 mL), 0.5 N aqueous citric acid (20 mL) and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a crude viscous oil. The crude oil was purified by flash chromatography (silica gel, 50% ethyl acetate/hexanes) to give the title compound (1.36 g, 95%) as a colorless oil.

Workup

  1. washwashed sequentially with saturated aqueous sodium bicarbonate (20 mL), 0.5 N aqueous citric acid (20 mL) and brine (20 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto yield a crude viscous oil
  6. customThe crude oil was purified by flash chromatography (silica gel, 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d06644afaa0d4da1bc59b9ca277d7bce
Source dataset
uspto-grants-2011_09
Patent number
US08022096B2

Reaction notes

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