Sulfuric Acid → HCID 86660716, compound

HRID 931900Notes

Reaction equation

HRID 931900 reaction equation
[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]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 8255IsobutyleneHCID 56591304HCID 56591304, compound

Product 1

HCID 86660716HCID 86660716, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-1dd36b7d633043d29250164fc8fc9fcf
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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