Hydrochloric Acid → HCID 15541405, compound

HRID 1823653Notes

Reaction equation

HRID 1823653 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.[K+].[Cl-].[Mg+2].[Cl-].[OH:14][C@@:15]([CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH2:24][CH2:25][CH3:26])[CH2:16]C(N1C=CN=C1)=O.Cl>C1COCC1>[OH:14][C@@:15]([CH2:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)([CH2:24][CH2:25][CH3:26])[CH2:16][C:3](=[O:5])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 68904488HCID 68904488, compound

Product 1

HCID 15541405HCID 15541405, compoundYield 67.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

Potassium monoethyl malonate (1.080 g, 6.348 mmole) was added to a suspension of magnesium chloride (0.5437 g, 5.713 mmole) and THF (4 mL) and the mixture was stirred at 40° C. for 2 hr. To this suspension was added the total amount of a solution of (R)-3-hydroxy-1-(1-imidazolyl)-3-(2-phenylethyl)hexane-1-one in THF obtained in Reference Example 3 at 40° C., and the mixture was stirred at 60° C. for 6 hr. After cooling to 0° C., 10% aqueous hydrochloric acid (4.4 g) was gradually added in a thin stream and the mixture was stirred at 0° C. for 15 min. After standing still, the mixture was partitioned and the aqueous layer was removed. Saturated brine (4 g) was added to the organic layer and the mixture was stirred for 15 min while maintaining the temperature. After standing still, the mixture was partitioned and the aqueous layer was removed. Anhydrous magnesium sulfate (1 g) was added to the organic layer and dried. Magnesium sulfate was filtered off and the obtained filtrate was concentrated under reduced pressure to give a crude product (1.45 g) of ethyl (R)-5-hydroxy-3-oxo-5-(2-phenylethyl)octanoate. This was purified by silica gel column chromatography to give ethyl (R)-5-hydroxy-3-oxo-5-(2-phenylethyl)octanoate (0.875 g, yield 67.5%).

Workup

  1. customobtained in Reference Example 3 at 40° C.
  2. stirringthe mixture was stirred at 60° C. for 6 hr
  3. temperatureAfter cooling to 0° C.
  4. stirringthe mixture was stirred at 0° C. for 15 min
  5. customthe mixture was partitioned
  6. customthe aqueous layer was removed
  7. additionSaturated brine (4 g) was added to the organic layer
  8. stirringthe mixture was stirred for 15 min
  9. temperaturewhile maintaining the temperature
  10. customthe mixture was partitioned
  11. customthe aqueous layer was removed
  12. additionAnhydrous magnesium sulfate (1 g) was added to the organic layer
  13. customdried
  14. filtrationMagnesium sulfate was filtered off
  15. concentrationthe obtained filtrate was concentrated under reduced pressure
  16. customto give a crude product (1.45 g) of ethyl (R)-5-hydroxy-3-oxo-5-(2-phenylethyl)octanoate
  17. customThis was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c405bf27c6284d3790408ebc999fa0f6
Source dataset
uspto-grants-2006_05
Patent number
US07038075B2

Reaction notes

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