Sulfuric Acid → (S)-ethyl 2-((3R,5R,6S)-3-(2-tert-butoxy-2-oxoethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanoate

HRID 931900ノート

反応式

HRID 931900 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:27][CH3:28])[C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:11](=[O:29])[C@@H:10]([CH2:30][C:31]([OH:33])=[O:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O.[CH3:39][C:40](=[CH2:42])[CH3:41]>C(Cl)Cl>[C:40]([O:32][C:31](=[O:33])[CH2:30][C@H:10]1[CH2:9][C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C@@H:13]([C:14]2[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)[N:12]([C@@H:21]([CH2:27][CH3:28])[C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:11]1=[O:29])([CH3:42])([CH3:41])[CH3:39]

参加物

5

反応物 3

HCID 1118Sulfuric AcidHCID 8255IsobutyleneHCID 56591304HCID 56591304、化合物

生成物 1

HCID 86660716(S)-ethyl 2-((3R,5R,6S)-3-(2-tert-butoxy-2-oxoethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanoate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of 1.14 g (2.3 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-1-oxobutan-2-yl)-2-oxopiperidin-3-yl)acetic acid (Example 3) in DCM (21.0 mL) was added sulfuric acid (0.247 mL, 4.63 mmol) followed by isobutylene (4.42 mL, 46.3 mmol) at −78° C. The reaction vessel was sealed and the mixture was slowly warmed to rt and vigorously stirred for 3 days. After cooling to −78° C., the tube was opened and the reaction was quenched with aqueous saturated NaHCO3 to pH 8. The organic solvent was removed under reduced pressure, and the remaining mixture was extracted (2×EtOAc). The combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (eluent: 20 to 35% EtOAc/hexanes) to provide the title compound as a foam.

後処理

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling to −78° C.
  3. customthe reaction was quenched with aqueous saturated NaHCO3 to pH 8
  4. customThe organic solvent was removed under reduced pressure
  5. extractionthe remaining mixture was extracted (2×EtOAc)
  6. washThe combined organic layers were washed with sat. NaCl solution
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by chromatography on silica gel (eluent: 20 to 35% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-1dd36b7d633043d29250164fc8fc9fcf
出典データセット
uspto-grants-2016_03
特許番号
US09296736B2

反応ノート

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