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

HRID 4503

反応式

HRID 4503 の反応式
[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]

参加物

5

反応物 3

HCID 1049PyridineHCID 6371PhosgeneHCID 5281078Mycophenolate Mofetil

生成物 1

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

試薬・触媒・溶媒 1

HCID 241Benzene溶媒2 回

反応条件

温度
25 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-ce801baf663247ddbe6aa39a88d06aae
出典データセット
uspto-grants-1988_02
特許番号
US04727069

関連ノート

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