Sodium Acetate → 5-[3-Chloro-4-(cyano-dimethyl-methyl)-phenyl]-3-cyclopentyl-3-hydroxy-pent-4-enoic acid

HRID 2387176Notes

Reaction equation

HRID 2387176 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[C:4]([Cl:13])[CH:3]=1.[CH:14]1([C@:19]([OH:26])([CH:24]=[CH2:25])[CH2:20][C:21]([OH:23])=[O:22])[CH2:18][CH2:17][CH2:16][CH2:15]1.CC([O-])=O.[Na+].[H][H]>CC(N(C)C)=O.CCO.CC([O-])=O.CC([O-])=O.[Pd+2].[OH-].[OH-].[Pd+2]>[Cl:13][C:4]1[CH:3]=[C:2]([CH:25]=[CH:24][C:19]([CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)([OH:26])[CH2:20][C:21]([OH:23])=[O:22])[CH:7]=[CH:6][C:5]=1[C:8]([C:9]#[N:10])([CH3:12])[CH3:11]

Participants

9

Reactant 4

HCID 517045Sodium AcetateHCID 587626012-(4-Bromo-2-chlorophenyl)-2-methylpropanenitrileHCID 58764151(3R)-3-cyclopentyl-3-hydroxypent-4-enoic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 690589925-[3-Chloro-4-(cyano-dimethyl-methyl)-phenyl]-3-cyclopentyl-3-hydroxy-pent-4-enoic acidYield 100%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 2-(4-bromo-2-chloro-phenyl)-2-methyl-propionitrile (0.61 g, 2.34 mmol), from step 4 of example B(22), (3R)-3-cyclopentyl-3-hydroxypent-4-enoic acid (0.43 g, 2.34 mmol, example C(14), Pd(OAc)2 (0.01 g, 5 mol %) and NaOAc (0.24 g, 2.93 mmol). in DMAC (5 mL) was heated at 90° C. overnight. The reaction mixture was cooled to room temperature and partitioned between 1N HCl and EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated to dark brown oil. Flash column chromatography (0% to 40% EtOAc in hexanes) gave a light brown oil. The oil was dissolved in EtOH (10 mL) and treated with Pd(OH)2 (0.23 g) The mixture was stirred under a balloon of hydrogen for 1 hour. The reaction mixture was filtered through a pad of celite washing with EtOAc. The filtrate was concentrated to an orange oil and purified by flash column chromatography to give the product as a yellow solid (0.47 g, 100%). 1H NMR (300 MHz, CDCl3): δ 1.4-1.72 (m, 10 H), 1.85 (s, 6 H), 2.11-2.18 (m, 1 H), 2.56-2.73 (m, 4 H), 7.10 (d, J=7.9 Hz, 1 H), 7.26 (s, 1 H), 7.36 (d, J=7.9 Hz, 1 H). ESIMS (MNa+): 364.

Workup

  1. custompartitioned between 1N HCl and EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dark brown oil
  5. customFlash column chromatography (0% to 40% EtOAc in hexanes) gave a light brown oil
  6. filtrationThe reaction mixture was filtered through a pad of celite
  7. washwashing with EtOAc
  8. concentrationThe filtrate was concentrated to an orange oil
  9. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-6c23e24216ca43cf87b6274dbbc224f8
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

Loading…