Diethyl Malonate → Diethyl (1-benzhydryl-3-azetidinyl)malonate

HRID 1177416Notes

Reaction equation

HRID 1177416 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH:14]([N:27]1[CH2:30][CH:29](S(C2C=CC(C)=CC=2)(=O)=O)[CH2:28]1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C)C=O>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([CH:29]1[CH2:30][N:27]([CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:28]1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 671126111-Benzhydryl-3-(toluene-4-sulfonyl)-azetidine

Product 1

HCID 11132697Diethyl (1-benzhydryl-3-azetidinyl)malonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (4.97 g, 0.129 mol) in 130 mL of anhydrous dimethyl formamide was added diethyl malonate (22.7 mL, 0.142 mol) dropwise at 0° C. and this reaction mixture was stirred at room temperature for 2 h. 1-Benzhydryl-3-(toluene-4-sulfonyl)-azetidine was added to it dropwise at 0° C. and reaction mixture was refluxed at 110° C. for 20 h. Excess sodium hydride was quenched with ammonium chloride, DMF was removed, and the reaction mixture was partitioned between chloroform and water; the aqueous layer was extracted with chloroform, the solvent was removed in vacuo, and purification by (neutral alumina) chromatography and 30% ethyl acetate/hexanes as eluent provided 2-(1-benzhydryl-azetidin-3-yl)-malonic acid diethyl ester. 1H-NMR (400 MHz, CDCl3), δ ppm 7.41-7.17 (m, 10H), 4.34 (s, 1H), 4.25-4.09 (m, 3H), 3.66 (d, 1H, J=3.66 Hz), 3.41-3.37 (m, 2H), 3.07-2.99 (m, 1H), 2.93-2.90 (m, 2H), 1.25-1.23 (m, 6H)

Workup

  1. customreaction mixture
  2. temperaturewas refluxed at 110° C. for 20 h
  3. customExcess sodium hydride was quenched with ammonium chloride, DMF
  4. customwas removed
  5. customthe reaction mixture was partitioned between chloroform and water
  6. extractionthe aqueous layer was extracted with chloroform
  7. customthe solvent was removed in vacuo, and purification by (neutral alumina) chromatography and 30% ethyl acetate/hexanes as eluent

Sources & evidence

ORD record
ord-5aa2a00ec2454d40bd1e82a0e2ce870e
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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