Tetrahydrofuran → HCID 68352804, compound

HRID 572482Notes

Reaction equation

HRID 572482 reaction equation
CC([Si](C1C=CC=CC=1)(C1C=CC=CC=1)[O:6][CH2:7][C@H:8]([C:10]1[N:11]([CH3:29])[C:12](=[O:28])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH3:27])[CH:21]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2)[OH:9])(C)C.[CH3:42][C:43](=[CH2:45])[CH3:44].CCCC[N+](CCCC)(CCCC)CCCC.[F-].O1CCCC1>ClCCl>[C:43]([O:9][C@@H:8]([C:10]1[N:11]([CH3:29])[C:12](=[O:28])[C:13]2[C:18]([C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH3:27])[CH:21]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][OH:6])([CH3:45])([CH3:44])[CH3:42]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8255IsobutyleneHCID 2724141Tetrabutylammonium FluorideHCID 86700718HCID 86700718, compound

Product 1

HCID 68352804HCID 68352804, compoundYield 43.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A −78° C. suspension of 3-((1S)-2-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-1-hydroxyethyl)-4-(3,4-dimethylphenyl)-2-methyl-1(2H)-isoquinolinone (12 mg, 0.021 mmol) and amberlyst 15 resin (6 mg, 0.036 mmol) in Dichloromethane (DCM) (290 μl) was treated with isobutylene until the volume approximately doubled. The reaction mixture was sealed and allowed to warm to ambient temperature. After 48 h, the reaction mixture was cooled to −78° C. and then opened to the atmosphere. The reaction mixture was filtered through a short pad of silica and rinsed with EtOAc. The filtrate was concentrated in vacuo. The residue was dissolved in Tetrahydrofuran (THF) (290 μl) and treated with 1.0 M TBAF in THF (145 μl, 0.145 mmol). After 2 h, the reaction mixture was filtered through a short pad of silica gel and washed with EtOAc. The filtrate was concentrated in vacuo and purified by reverse phase hplc to afford the title compound (6 mg, 0.016 mmol, 43.6% yield) as a white solid: Rt=1.02, ES+ MS: 380 (M+1).

Workup

  1. customThe reaction mixture was sealed
  2. temperaturethe reaction mixture was cooled to −78° C.
  3. filtrationThe reaction mixture was filtered through a short pad of silica
  4. washrinsed with EtOAc
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionThe residue was dissolved in Tetrahydrofuran (THF) (290 μl)
  7. waitAfter 2 h
  8. filtrationthe reaction mixture was filtered through a short pad of silica gel
  9. washwashed with EtOAc
  10. concentrationThe filtrate was concentrated in vacuo
  11. custompurified by reverse phase

Sources & evidence

ORD record
ord-59fa625af3fe49678da4f932c09a8cc9
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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