Cesium carbonate → 4'-[(1S,2R)-2-(2-Hydroxyethyl)cycloprop-1-yl]biphenyl-4-carbonitrile

HRID 515048Notes

Reaction equation

HRID 515048 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:10][C@@H:9]2[CH2:11][CH2:12][OH:13])=[CH:4][CH:3]=1.[C:14]([C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1)#[N:15].C([O-])([O-])=O.[Cs+].[Cs+]>C(O)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:13][CH2:12][CH2:11][C@H:9]1[CH2:10][C@@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([C:19]2[CH:20]=[CH:21][C:16]([C:14]#[N:15])=[CH:17][CH:18]=2)=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343264-Cyanophenylboronic acidHCID 684071222-[(1R,2S)-2-(4-Bromophenyl)cycloprop-1-yl]ethanol

Product 1

HCID 684076744'-[(1S,2R)-2-(2-Hydroxyethyl)cycloprop-1-yl]biphenyl-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolvent

Procedure

A solution of the product of Example 28E (2-[(1R,2S)-2-(4-bromophenyl)cycloprop-1-yl]ethanol), 4-cyanophenylboronic acid [CAS 126747-14-6] (2 equivalents), Pd(PPh3)2Cl2, and Cs2CO3 in isopropanol under N2 was stirred at reflux overnight. The mixture was partitioned between ethyl acetate and H2O. The organic layer was washed with saturated aqueous NaHCO3 and then with brine. The organic layer was then dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the resulting residue was purified by chromatography on silica gel eluted with 4:1 hexanes/ethyl acetate to provide the title compound.

Workup

  1. temperatureat reflux overnight
  2. customThe mixture was partitioned between ethyl acetate and H2O
  3. washThe organic layer was washed with saturated aqueous NaHCO3
  4. dry with materialThe organic layer was then dried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe resulting residue was purified by chromatography on silica gel
  8. washeluted with 4:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-4d5003c5387e48bf9c8ea8063b9ce60a
Source dataset
uspto-grants-2015_08
Patent number
US09108948B2

Reaction notes

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