3-Cyanophenylboronic acid → 1,1-Dimethylethyl {2-[(3'-cyano-4-biphenylyl)oxy]ethyl}(4,4-dimethylcyclohexyl)carbamate

HRID 471843Notes

Reaction equation

HRID 471843 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][CH2:20][CH2:21][N:22]([CH:30]2[CH2:35][CH2:34][C:33]([CH3:37])([CH3:36])[CH2:32][CH2:31]2)[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:15][CH:14]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]([CH:30]3[CH2:31][CH2:32][C:33]([CH3:37])([CH3:36])[CH2:34][CH2:35]3)[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:15][CH:14]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 27343253-Cyanophenylboronic acidHCID 582762401,1-Dimethylethyl {2-[(4-bromophenyl)oxy]ethyl}(4,4-dimethylcyclohexyl)carbamate

Product 1

HCID 671599511,1-Dimethylethyl {2-[(3'-cyano-4-biphenylyl)oxy]ethyl}(4,4-dimethylcyclohexyl)carbamate

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

A mixture of m-cyanophenyl boronic acid (0.086 g; 0.59 mmol), 1,1-dimethylethyl {2-[(4-bromophenyl)oxy]ethyl}(4,4-dimethylcyclohexyl)carbamate (0.250 g; 0.59 mmol; Example V-8), PdCl2(dppf).CH2Cl2, 2M Na2CO3 (4 mL) and DME (4 mL) was sparged 5 min with N2 and then heated to 80° C. for 5 h. Upon cooling, the mixture was diluted with EtOAc, washed with water and the washing was back-extracted with EtOAc (×2). Combined organics were washed (water, brine), dried over Na2SO4, adsorbed onto a minimal amount of silica gel and purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless gum. 1H NMR (400 MHz, CDCl3) δ 0.92 (s, 3H), 0.94 (s, 3H, partially overlapping 0.92), 1.21-1.87 (m, 17H), 3.45-3.63 (m, 2H), 3.88 (br. s, 1H), 4.10 (br. s, 2H), 7.00 (m, 2H), 7.49 (m, 2H), 7.52 (d, J=7.8 Hz, 1H; partially overlapping 7.49), 7.58 (d, J=7.6 Hz, 1H), 7.77 (partially resolved ddd, Jortho=7.8 Hz, 1H), 7.82 (unresolved dd, 1H).

Workup

  1. customCH2Cl2, 2M Na2CO3 (4 mL) and DME (4 mL) was sparged 5 min with N2
  2. temperatureUpon cooling
  3. additionthe mixture was diluted with EtOAc
  4. washwashed with water
  5. extractionthe washing was back-extracted with EtOAc (×2)
  6. washCombined organics were washed (water, brine)
  7. dry with materialdried over Na2SO4
  8. custompurified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-16aec7a376aa49a7a1e22bc892fcc066
Source dataset
uspto-grants-2014_01
Patent number
US08633175B2

Reaction notes

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