Pyridine → morpholinoethyl E-6-(1,3-dihydro-4-carbamoyloxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate

HRID 4503

Reaction equation

HRID 4503 reaction equation
[OH:1][C:2]1[C:10]([CH2:11]/[CH:12]=[C:13](\[CH3:27])/[CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:17])=[C:9]([O:28][CH3:29])[C:8]([CH3:30])=[C:7]2[C:3]=1[C:4](=[O:31])[O:5][CH2:6]2.[N:32]1[CH:37]=CC=CC=1.C(Cl)(Cl)=[O:39]>C1C=CC=CC=1>[C:37]([O:1][C:2]1[C:10]([CH2:11]/[CH:12]=[C:13](\[CH3:27])/[CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:17])=[C:9]([O:28][CH3:29])[C:8]([CH3:30])=[C:7]2[C:3]=1[C:4](=[O:31])[O:5][CH2:6]2)(=[O:39])[NH2:32]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6371PhosgeneHCID 5281078Mycophenolate Mofetil

Product 1

HCID 67854272morpholinoethyl E-6-(1,3-dihydro-4-carbamoyloxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of 500 mgs of morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate in 10 ml of benzene cooled in an ice bath is added 0.1 ml of pyridine and 6 ml of a 12.5% solution of phosgene in benzene. The solution is stirred at 25° C. overnight, the precipitate filtered off and solvent removed from the filtrate under reduced pressure. The residue is dissolved in 5 ml of tetrahydrofuran and to this solution is added dropwise a solution of ammonia in tetrahydrofuran until the reaction is complete. The mixture is poured into water and extracted with ethyl acetate. The organic solution is dried over magnesium sulfate and evaporated to an oil which is chromatographed on silica gel, eluting with a 50:1 mixture of dichloromethane and methanol. The purified product is stirred with a mixture of ether and hexane and filtered giving morpholinoethyl (E)-6-(1,3-dihydro-4-carbamoyloxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.

Workup

  1. filtrationthe precipitate filtered off
  2. customsolvent removed from the filtrate under reduced pressure
  3. dissolutionThe residue is dissolved in 5 ml of tetrahydrofuran and to this solution
  4. additionis added dropwise a solution of ammonia in tetrahydrofuran until the reaction
  5. additionThe mixture is poured into water
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic solution is dried over magnesium sulfate
  8. customevaporated to an oil which
  9. customis chromatographed on silica gel
  10. washeluting with a 50:1 mixture of dichloromethane and methanol
  11. stirringThe purified product is stirred with a mixture of ether and hexane
  12. filtrationfiltered

Sources & evidence

ORD record
ord-ce801baf663247ddbe6aa39a88d06aae
Source dataset
uspto-grants-1988_02
Patent number
US04727069

Linked notes

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