Nitrogen → 1,1-Dimethylethyl (2-{[4'-(acetylamino)-4-biphenylyl]oxy}ethyl)(4,4-dimethylcyclohexyl)carbamate

HRID 471842Notes

Reaction equation

HRID 471842 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][N:11]([CH:19]2[CH2:24][CH2:23][C:22]([CH3:26])([CH3:25])[CH2:21][CH2:20]2)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[C:27]([NH:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)(=[O:29])[CH3:28].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].N#N>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].COCCOC>[C:27]([NH:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][N:11]([CH:19]3[CH2:20][CH2:21][C:22]([CH3:25])([CH3:26])[CH2:23][CH2:24]3)[C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[CH:4][CH:3]=2)=[CH:33][CH:32]=1)(=[O:29])[CH3:28]

Participants

8

Reactant 5

HCID 947NitrogenHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27346574-Acetamidophenylboronic acidHCID 582762401,1-Dimethylethyl {2-[(4-bromophenyl)oxy]ethyl}(4,4-dimethylcyclohexyl)carbamate

Product 1

HCID 582765751,1-Dimethylethyl (2-{[4'-(acetylamino)-4-biphenylyl]oxy}ethyl)(4,4-dimethylcyclohexyl)carbamate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 1,1-dimethylethyl {2-[(4-bromophenyl)oxy]ethyl}(4,4-dimethylcyclohexyl)carbamate (0.085 g; 0.20 mmol; Example V-8), [4-(acetylamino)phenyl]boronic acid (0.040 g; 0.22 mmol), PdCl2(dppf).CH2Cl2 (0.005 g; 0.006 mmol), Na2CO3 (2 mL of a 2M solution) and DME (2 mL) was sparged with N2 for 10 minutes at room temperature and heated at 80° for 1 h (until consumption of the aryl bromide, as judged by LC/MS). Upon cooling, the mixture was partitioned between EtOAc/H2O, layers were separated and the aqueous layer was extracted with EtOAc (×2). Combined organics were washed (brine), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a pale yellow solid. LC/MS (method A) tR 3.29 min, m/z 481 (M+H, 53%), 381 ([M−Boc]+H, 100%).

Workup

  1. temperatureheated at 80° for 1 h (
  2. customuntil consumption of the aryl bromide
  3. temperatureUpon cooling
  4. customthe mixture was partitioned between EtOAc/H2O, layers
  5. customwere separated
  6. extractionthe aqueous layer was extracted with EtOAc (×2)
  7. washCombined organics were washed (brine)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-d8f8417d439c40f6a7439a3c877b86a3
Source dataset
uspto-grants-2014_01
Patent number
US08633175B2

Reaction notes

Loading…