1,1'-Carbonyldiimidazole → HCID 66732596, compound

HRID 1963589Notes

Reaction equation

HRID 1963589 reaction equation
[C:1]([OH:7])(=O)[CH2:2][C:3]([OH:5])=[O:4].[CH2:8]([K])[CH3:9].[Mg+2].[Cl-].[Cl-].[CH3:14][O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21](C(O)=O)[CH2:20][CH:19]1[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:30][CH:29]=1)=[O:17].C(N1C=CN=C1)(N1C=CN=C1)=O>C(OCC)C.O.C1COCC1>[CH2:8]([O:5][C:3](=[O:4])[CH2:2][C:1]([CH:21]1[CH2:22][CH2:23][N:18]([C:16]([O:15][CH3:14])=[O:17])[CH:19]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:32][CH:33]=2)[CH2:20]1)=[O:7])[CH3:9]

Participants

8

Reactant 4

HCID 682631,1'-Carbonyldiimidazole2×HCID 5360315Magnesium ChlorideHCID 66732094HCID 66732094, compound2×HCID 178461627HCID 178461627, compound

Product 1

HCID 66732596HCID 66732596, compoundYield 79.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Ethyl potassium malonate (2.414 g, 14.18 mmol) and MgCl2 (1.125 g, 11.82 mmol) were added to dry THF (75 mL). The reaction flask was stirred vigorously for 4 h at 50° C. (flask 1). 1-(Methoxycarbonyl)-2-(4-(methylsulfonyl)benzyl)piperidine-4-carboxylic acid (4.2 g, 11.82 mmol) (reference compound 51) and carbonyldiimidazole (2.87 g, 17.73 mmol) were added to dry THF (75 mL) at room temperature (flask 2). More di(1H-imidazol-1-yl)methanone (0.5 g) was added and after 2 h the contents of flask 2 was added to flask 1 at room temperature and stirred overnight. The reaction mixture was dissolved between water and diethyl ether. The organic phase was isolated, dried with Na2SO4, filtered through celite and the solvent was evaporated. Chromatography using the Biotage equipment. Gradient eluation using ethylacetate-heptane, started 10-90 and ended 100-0. Methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)benzyl)piperidine-1-carboxylate (3.99 g, 79%) was isolated.

Workup

  1. additionwas added to flask 1 at room temperature
  2. stirringstirred overnight
  3. customThe organic phase was isolated
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered through celite
  6. customthe solvent was evaporated

Sources & evidence

ORD record
ord-21d067e4e3e048dcb905d87c7139fd79
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…