Pyridine → HCID 86629197, compound

HRID 2063492Notes

Reaction equation

HRID 2063492 reaction equation
[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@@H:12]1[C:13]([OH:15])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[Cl-].[Mg+2].[Cl-].[C:33](OC(C)(C)C)(=[O:38])[CH2:34][C:35]([CH3:37])=[O:36].N1C=CC=CC=1>ClCCl.CCOC(C)=O>[C:33](=[C:34]([C:35](=[O:36])[CH3:37])[C:13]([C@H:12]1[CH2:16][CH2:17][CH2:18][N:11]1[C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])=[O:15])=[O:38]

Participants

9

Reactant 6

HCID 1049PyridineHCID 6228DimethylformamideHCID 15538Tert-butyl acetoacetateHCID 65578Oxalyl chlorideHCID 1112081-benzyl hydrogen (R)-pyrrolidine-1,2-dicarboxylateHCID 5360315Magnesium Chloride

Product 1

HCID 86629197HCID 86629197, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (+)-carbobenzyloxy-D-proline (10 g, 40 mmol) in dichloromethane (250 mL) was added oxalyl chloride (6.9 mL, 80 mmol) followed by dimethyl formamide (15 μL, 0.2 mmol). The reaction mixture was then stirred for 2 h and concentrated in vacuo. The resulting acid chloride in dichloromethane (50 mL) was added to a mixture of magnesium chloride (4 g, 40 mmol) and tert-butyl acetoacetate (6.5 mL, 4 mmol) in pyridine (6.5 mL, 80 mmol) and dichloromethane (50 mL) at 0° C. and stirred for 30 min. The reaction mixture was then stirred at room temperature for 16 h and then diluted with EtOAc (25 mL). The organic layer was washed with 10% HCl solution (1×250 mL), saturated NaHCO3 solution (1×250 mL) and then brine (1×250 mL). The separated organic layer was then dried over Na2SO4 and concentrated in vacuo to afford (2R)-benzyl 2-(2-(carbonyl)-3-oxobutanoyl)pyrrolidine-1-carboxylate. LCMS: 6.51 min, calculated: 389, found (MH+): 390.

Workup

  1. concentrationconcentrated in vacuo
  2. stirringstirred for 30 min
  3. stirringThe reaction mixture was then stirred at room temperature for 16 h
  4. washThe organic layer was washed with 10% HCl solution (1×250 mL), saturated NaHCO3 solution (1×250 mL)
  5. dry with materialThe separated organic layer was then dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-101989f5b25c4ee4b6fbe987dce29144
Source dataset
uspto-grants-2012_10
Patent number
US08288371B2

Reaction notes

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