Chloride → HCID 21255120, compound

HRID 636572Notes

Reaction equation

HRID 636572 reaction equation
[Cl-].[Mg+2].[Cl-].[C:4]([O:11][CH3:12])(=[O:10])[CH2:5][C:6]([O:8][CH3:9])=[O:7].[Cl-].[N:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]2[N:28]3[C:23]([CH2:24][CH2:25][CH2:26][CH2:27]3)=[C:22]([C:29](O)=[O:30])[CH:21]=2)[CH:15]=1.Cl>C(#N)C.O.C(N(CC)CC)C>[CH3:9][O:8][C:6]([CH:5]([C:29](=[O:30])[C:22]1[CH:21]=[C:20]([C:16]2[CH:15]=[N:14][CH:19]=[CH:18][CH:17]=2)[N:28]2[C:23]=1[CH2:24][CH2:25][CH2:26][CH2:27]2)[C:4]([O:11][CH3:12])=[O:10])=[O:7]

Participants

9

Reactant 5

HCID 312ChlorideHCID 313Hydrochloric AcidHCID 7943Dimethyl malonateHCID 5360315Magnesium ChlorideHCID 21255107HCID 21255107, compound

Product 1

HCID 21255120HCID 21255120, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

6.8 cm3 of triethylamine are added dropwise to a suspension of 1.4 g of magnesium chloride in 16 cm3 of acetonitrile under argon, followed, after 5 minutes, by 2.9 cm3 of dimethyl malonate. The resulting white suspension is then stirred at ambient temperature under argon for 1 hour. To this suspension is then added, via a cannula, a suspension, prepared beforehand from 6.3 g of the chloride of 3-(3-pyridyl)-5,6,7,8-tetrahydroindolizine-1-carboxylic acid in 36 cm3 of acetonitrile under argon, to which 2.8 cm3 of triethylamine has been added. The resulting brick-red suspension is stirred at ambient temperature under argon for 18 hours and is then cooled to 0° C. and treated dropwise with 7 cm3 of concentrated hydrochloric acid. The resulting mixture is diluted with 15 cm3 of distilled water and separated and then the aqueous phase is extracted 6 times with 50 cm3 of dichloromethane. The organic extracts are combined and dried over magnesium sulphate and then concentrated at reduced pressure (2.7 kPa). 8.1 g of methyl 2-(methoxycarbonyl)-3-oxo-3-[3-(3-pyridyl)-5,6,7,8-tetrahydro-1-indolizinyl]propionate are thus obtained in the form of a beige crystalline solid melting at 146-150° C. (Rf=0.65; thin layer chromatography on silica gel; eluent: 10/90 by volume mixture of methanol and of dichloromethane).

Workup

  1. additionTo this suspension is then added, via a cannula
  2. stirringThe resulting brick-red suspension is stirred at ambient temperature under argon for 18 hours
  3. temperatureis then cooled to 0° C.
  4. customseparated
  5. extractionthe aqueous phase is extracted 6 times with 50 cm3 of dichloromethane
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated at reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-171d90d4e1014fed8d4d244b5373e780
Source dataset
uspto-grants-2001_02
Patent number
US06194426B1

Reaction notes

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