Magnesium Chloride → HCID 54095040, compound

HRID 1449775Notes

Reaction equation

HRID 1449775 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C@@H:14]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[CH2:15][C:16]([OH:18])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]([O:30][C:31](=[O:36])[CH2:32]C([O-])=O)([CH3:29])([CH3:28])[CH3:27].[K+].[Cl-].[Mg+2].[Cl-]>C(#N)C>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C@@H:14]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[CH2:15][C:16](=[O:18])[CH2:32][C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:36])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 5360315Magnesium ChlorideHCID 23662309HCID 23662309, compoundHCID 54335229HCID 54335229, compound

Product 1

HCID 54095040HCID 54095040, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
10 °C

Procedure

Into a one-liter four-necked flask were poured 43.9 g (0.125 mole) of (3R)-5-benzyloxycarbonylamino-3-(2-tetrahydropyranyloxy)pentanoic acid (2-c) obtained in the above process B and 290 ml of acetonitrile. Furthermore, 19.6 g (0.121 mole) of N,N'-carbonyldiimidazole was added to the contents over a period of 15 minutes in a nitrogen stream with stirring. Gas evolution was observed. Approximately 30 minutes later the gas evolution was nearly complete. Then, the contents were cooled to approximately 10° C., and 35.2 g (0.178 mole) of potassium malonate tert-butyl ester and next 11.4 g (0.119 mole) of magnesium chloride were separately added thereto. After stirring for 1 hour at the same temperature, the contents were heated to 50° C. and allowed to react for 2 hours. After removing acetonitrile by distillation, 150 ml of ethyl acetate and 200 ml of a 5 wt % aqueous hydrochloric acid solution were added to thereby adjust the pH to 4.5. After separating the aqueous layer, the organic layer was neutralized by adding 25 ml of a 5 wt % aqueous sodium bicarbonate solution. The organic layer was washed with saturated sodium chloride solution and then dried with magnesium sulfate. The solvent was then removed by distillation, to thereby obtain 72.3 g of a crude oily product. The crude product was purified with a silica gel column using hexane/ethyl acetate=1/1 as an eluent to obtain the intended oily product (1). The yield was 57.8 g (79%).

Workup

  1. customApproximately 30 minutes
  2. stirringAfter stirring for 1 hour at the same temperature
  3. temperaturethe contents were heated to 50° C.
  4. customto react for 2 hours
  5. customAfter removing acetonitrile
  6. distillationby distillation, 150 ml of ethyl acetate and 200 ml of a 5 wt % aqueous hydrochloric acid solution
  7. additionwere added
  8. customAfter separating the aqueous layer
  9. additionby adding 25 ml of a 5 wt % aqueous sodium bicarbonate solution
  10. washThe organic layer was washed with saturated sodium chloride solution
  11. dry with materialdried with magnesium sulfate
  12. customThe solvent was then removed by distillation
  13. customto thereby obtain 72.3 g of a crude oily product
  14. customThe crude product was purified with a silica gel column

Sources & evidence

ORD record
ord-e4c7e4e511ca414e8ce3bbfae577d086
Source dataset
uspto-grants-1997_02
Patent number
US05599954

Reaction notes

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