Pyridine → {2-[4-(3-Chloro-4-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 474736Notes

Reaction equation

HRID 474736 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].[C:15]([O:19][C:20](=[O:31])[NH:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C.N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:15]([O:19][C:20](=[O:31])[NH:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][C:4]2[CH:5]=[CH:6][C:7]([C:8]([F:11])([F:10])[F:9])=[C:2]([Cl:1])[CH:3]=2)=[CH:26][CH:25]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 37729583-Chloro-4-(trifluoromethyl)benzeneboronic acidHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 67774227{2-[4-(3-Chloro-4-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl esterYield 34%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

Entire reaction was performed under dry air using syringe septa technique. 4 Å molecular sievies were added to a stirred solution of 3-chloro-4-(trifluoromethyl) phenylboronic acid (0.021 mol, 2 eq) and [2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert butyl ester (0.011 mol, 1 eq) in dry DCM (105 ml) at ambient temperature in a flame dried flask flushed with dry air. The reaction was stirred for 15 min. After that, copper (II) acetate (0.011 mol, 1.01 eq), triethylamine (0.053 mol, 5 eq) and pyridine (0.053 mol, 5 eq) were added in succession and the reaction was stirred for 50 hours. The reaction mixture was sequential washed with 0.5 M HCl (4×250 ml), water (3×150 ml) and brine (1×150 ml). Organic layers were combined, dried over Na2SO4/MgSO4, filtered and evaporated. Crude product was purified on Biotage SP1 Snap Si 100; 40 ml/min in the gradient of EtOAc in cyclohexan: 0-30% in 25 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product {2-[4-(3-chloro-4-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (3.703 mmol, yield=34%, purity=89%). [M+H]+=360.22 1H NMR (300 MHz, CDCl3) δ/ppm 1.42 (s, 9H), 2.75-2.84 (m, 2H), 3.31-3.43 (m, 2H), 4.55 (br. s., 1H), 6.84-6.90 (m, 1H), 6.94-7.01 (m, 2H), 7.02-7.06 (m, 1H), 7.18-7.23 (m, 3H), 7.55-7.61 (m, 1H)

Workup

  1. customEntire reaction
  2. customunder dry air
  3. customdried flask
  4. customflushed
  5. customwith dry air
  6. stirringthe reaction was stirred for 50 hours
  7. washThe reaction mixture was sequential washed with 0.5 M HCl (4×250 ml), water (3×150 ml) and brine (1×150 ml)
  8. dry with materialdried over Na2SO4/MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customCrude product was purified on Biotage SP1 Snap Si 100
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-2ba7b83b29bf4ee1bf1edb97658abac6
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

Loading…