Sodium Carbonate → (1S,2R)-4'-(2-Hydroxy-1-isopropyl-4-pyridin-3-yl-butoxy)biphenyl-3-carbonitrile

HRID 380003Notes

Reaction equation

HRID 380003 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].Br[C:13]1[CH:18]=[CH:17][C:16]([O:19][C@H:20]([C@H:24]([OH:33])[CH2:25][CH2:26][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)[CH:21]([CH3:23])[CH3:22])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:33][C@H:24]([CH2:25][CH2:26][C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1)[C@H:20]([CH:21]([CH3:23])[CH3:22])[O:19][C:16]1[CH:17]=[CH:18][C:13]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:1]#[N:2])[CH:4]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 57267460(3S,4R)-3-(4-bromophenyloxy)-2-methyl-6-(3-pyridyl)hexan-4-ol

Product 1

HCID 57308717(1S,2R)-4'-(2-Hydroxy-1-isopropyl-4-pyridin-3-yl-butoxy)biphenyl-3-carbonitrileYield 56.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

Prepared according to the method described in Example 12b) from 3-cyanobenzeneboronic acid (0.40 g), (3S,4R)-3-(4-bromophenyloxy)-2-methyl-6-(3-pyridyl)hexan-4-ol (0.90 g, Example 61d)), 2M aqueous sodium carbonate (2.72 ml) and tetrakis(triphenylphosphine)palladium(0) (0.160 g) in ethanol (4 ml). The reaction mixture was heated at 90° C. for 4 hours. After cooling, the solution was poured onto water, and extracted with ethyl acetate. The combined extracts were washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, dissolved in dichloromethane, filtered and purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give the title compound as a gum (0.54 g).

Workup

  1. customPrepared
  2. temperatureAfter cooling
  3. additionthe solution was poured onto water
  4. extractionextracted with ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. dissolutiondissolved in dichloromethane
  10. filtrationfiltered
  11. custompurified by normal-phase HPLC
  12. washeluting with a gradient of 0-25% ethanol in dichloromethane

Sources & evidence

ORD record
ord-525a06f970524d28ad45d225d753643a
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

Loading…