Bis(tributyltin) oxide → HCID 68754366, compound

HRID 333293Notes

Reaction equation

HRID 333293 reaction equation
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:13][C:14]([C:16]2([CH2:21][C:22]([O:24]CC)=[O:23])[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:15])[C:9]([O:11]C)=[O:10])=[CH:3][CH:2]=1.CCCC[Sn](O[Sn](CCCC)(CCCC)CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1>[C:1]1([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([NH:13][C:14]([C:16]2([CH2:21][C:22]([OH:24])=[O:23])[CH2:17][CH2:18][CH2:19][CH2:20]2)=[O:15])[C:9]([OH:11])=[O:10])=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 16682746Bis(tributyltin) oxideHCID 68748579HCID 68748579, compound

Product 1

HCID 68754366HCID 68754366, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (R)-methyl 3-(biphenyl-4-yl)-2-(1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxamido)propanoate (135.5 mg, 0.310 mmol) in toluene (3.1 ml), bis(tributyltin) oxide (1.578 ml, 3.10 mmol) was added at room temperature under nitrogen. The reaction mixture was allowed to stir at 90° C. for 15 hr and then 100° C. for 26 hr. The reaction mixture was cooled to room temperature, 10% KFaq (2 ml) was added. The suspension was vigorously stirred for 1 hr, the solution was filtered, and the organic layer and the aqueous layer were separated. To the aqueous layer, 10% citric acid aq was added. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and the obtained product was treated with 1M LiOH (0.5 ml) in THF (0.5 ml) and MeOH (0.1 ml) for 17 hr. The reaction mixture was acidified with 1M HCl to pH 3. The product was extracted with EtOAc, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue was purified twice by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) and then solidified in DCM/heptane to give (R)-3-(biphenyl-4-yl)-2-(1-(carboxymethyl)cyclopentanecarboxamido)propanoic acid (12.4 mg); Retention time=1.63 minutes (condition A); MS (m+1)=396.0; 1H NMR (400 MHz, DMSO-d6, mixture of rotamers) δ ppm 1.45-1.50 (m, 6H) 1.95-2.00 (m, 2H) 2.39-2.62 (m, 2H) 2.84-3.12 (m, 2H) 4.40-4.46 (m, 1H) 7.30-8.15 (m, 10H) 12.25 (br s, 2H); HRMS (ES+) m/z for C23H25NNaO5 [M+Na]+ calcd 418.16304. found 418.1632.

Workup

  1. wait100° C. for 26 hr
  2. temperatureThe reaction mixture was cooled to room temperature
  3. addition10% KFaq (2 ml) was added
  4. stirringThe suspension was vigorously stirred for 1 hr
  5. filtrationthe solution was filtered
  6. customthe organic layer and the aqueous layer were separated
  7. additionTo the aqueous layer, 10% citric acid aq was added
  8. extractionThe aqueous layer was extracted with EtOAc
  9. washThe combined organic layer was washed with brine
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe obtained residue was purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)
  14. additionthe obtained product was treated with 1M LiOH (0.5 ml) in THF (0.5 ml) and MeOH (0.1 ml) for 17 hr
  15. extractionThe product was extracted with EtOAc
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customThe obtained residue was purified twice by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-f8a997f5dff94f7787f0000825ae689f
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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