Diethyl Malonate → HCID 67099938, compound

HRID 1868897Notes

Reaction equation

HRID 1868897 reaction equation
[Mg+2].[Cl-].[Cl-].[C:4]([O:12][CH2:13][CH3:14])(=[O:11])[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].[Cl:15][C:16]1[CH:17]=[C:18]([C:23]2([C:29](O)=[O:30])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:19]=[CH:20][C:21]=1[F:22].S(Cl)(Cl)=O>C(#N)C>[Cl:15][C:16]1[CH:17]=[C:18]([C:23]2([C:29]([CH:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:4]([O:12][CH2:13][CH3:14])=[O:11])=[O:30])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[CH:19]=[CH:20][C:21]=1[F:22]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 24386Thionyl ChlorideHCID 5360315Magnesium ChlorideHCID 67099774HCID 67099774, compound

Product 1

HCID 67099938HCID 67099938, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

MgCl2 (2.39 g, 25.1 mmol) was added to diethyl malonate (3.45 mL, 22.8 mmol) in ACN (45.7 mL) after cooling the reaction mixture to 0° C. TEA (6.36 mL, 45.7 mmol) was then added dropwise, and the reaction mixture was warmed to ambient temperature and stirred for 2 hours. 4-(3-Chloro-4-fluorophenyl)-tetrahydro-pyran-4-carboxylic acid (5.61 g, 21.7 mmol) was converted to the acid chloride by reaction with thionyl chloride at 70° C. for 1 hour. The acid chloride reaction mixture was concentrated, dissolved in ACN, and added dropwise to the initial reaction mixture. The resulting mixture was stirred at ambient temperature for 2 hours and then quenched with water, acidified with 5N HCl, diluted with 100 mL of diethyl ether, added to a separatory funnel, partitioned with water, washed 2 times with 50 mL of water, separated, dried over Na2SO4, and concentrated in vacuo to give the title (3.87 g) after flash chromatography. MS m/e=401 (M+H)+.

Workup

  1. temperaturethe reaction mixture was warmed to ambient temperature
  2. concentrationwas concentrated
  3. dissolutiondissolved in ACN
  4. additionadded dropwise to the initial
  5. customreaction mixture
  6. stirringThe resulting mixture was stirred at ambient temperature for 2 hours
  7. customquenched with water
  8. additiondiluted with 100 mL of diethyl ether
  9. additionadded to a separatory funnel
  10. custompartitioned with water
  11. washwashed 2 times with 50 mL of water
  12. customseparated
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated in vacuo
  15. customto give the title (3.87 g) after flash chromatography

Sources & evidence

ORD record
ord-cff01d982fd74383ad79f54e218351f2
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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