1,2-Dichloroethane → 1-Tert-butyloxycarbonyl-cis-2-{[methoxy(methyl)amino]carbonyl}-5-phenylpyrrolidine

HRID 1162828Notes

Reaction equation

HRID 1162828 reaction equation
[C:1]([N:8]1[C@@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1C=C[C:25]2[N:30]([OH:31])N=NC=2C=1.[CH2:32](Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:4]([O:3][C:1]([N:8]1[C@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH2:13][C@@H:9]1[C:10]([N:30]([O:31][CH3:32])[CH3:25])=[O:12])=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2755972(2S,5R)-1-[(tert-butoxy)carbonyl]-5-phenylpyrrolidine-2-carboxylic acid

Product 1

HCID 866174771-Tert-butyloxycarbonyl-cis-2-{[methoxy(methyl)amino]carbonyl}-5-phenylpyrrolidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of racemic N-Boc-cis-5-phenylproline (2 g, 6.865 mmol) in DMF (35 mL) was added HOBt (1.05 g, 6.87 mmol), EDC (1.97 g, 10.3 mmol), O, N-dimethylhydroxylamine hydrochloride (1.00 g, 10.3 mmol) and DIEA dropwise (1.33 mL, 10.3 mmol). The reaction was stirred at ambient temperature for 30 min and then partitioned between ethyl acetate and water. The EtOAc layer was separated and washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 50:50 ethyl acetate and hexane. Collection and concentration of appropriate fractions provided the title compound. HPLC RT=3.46 min, 86% at 215 nm (Method A); ES MS (M+H)=335.3.

Workup

  1. custompartitioned between ethyl acetate and water
  2. customThe EtOAc layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-ef74f34f04034cfabecba5040835f3cc
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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