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

HRID 474716Notes

Reaction equation

HRID 474716 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[C:14]([O:18][C:19](=[O:30])[NH:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)([CH3:17])([CH3:16])[CH3:15].N1C=CC=CC=1>C(Cl)Cl.CCOCC.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:14]([O:18][C:19](=[O:30])[NH:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=2)=[CH:25][CH:24]=1)([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 3

HCID 1049PyridineHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 67772730{2-[4-(3-Trifluoromethyl-phenoxy)-phenyl]ethyl}-carbamic acid tert-butyl esterYield 29.5%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

4 Å molecular sieves were added to a stirred solution of 3-(trifluoromethyl)phenylboronic acid (2.4 g, 12.643 mmol, 2 eq) and [2-(4-Hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester (1.5 g, 6.321 mmol, 1 eq) in dry DCM (68.7 ml) at ambient temperature in a dark flask flushed with dry air. The reaction mixture was stirred for 10 min with a drying tube attached. Copper (II) acetate (1.16 g, 6.385 mmol, 1.01 eq), TEA (4.4 ml, 31.609 mmol, 5 eq) and pyridine (2.55 ml, 31.609 mmol, 5 eq) were added and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with 50 ml of Et2O, filtered through celite and washed with 0.5 M HCl. Organic layer was dried over anhydrous Na2SO4, filtered and evaporated to give a crude product. Crude product was purified via Biotage SP-1 Snap Si 50 g; 40 mil/min; in the gradient of EtOAc in Cy: 3% for 1.5 CV, 3-25% for 12 CV; 25-40% for 8 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product {2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (710 mg, yield=22.4%, purity=76%). [M+H]+=382.40 1H NMR (300 MHz; CDCl3) δ/ppm 1.43 (s, 9H), 2.77 (t, J=7.0 Hz, 2H), 3.37 (q, J=6.5 Hz, 2H), 4.58 (br. s., 1H), 6.92-6.97 (m, 1H), 7.06-7.22 (m, 5H), 7.28-7.33 (m, 1H), 7.34-7.45 (m, 1H)

Workup

  1. customflushed
  2. customwith dry air
  3. stirringthe reaction mixture was stirred at ambient temperature overnight
  4. filtrationfiltered through celite
  5. washwashed with 0.5 M HCl
  6. dry with materialOrganic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give a crude product
  10. customCrude product was purified via Biotage SP-1 Snap Si 50 g
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-910eb19376624de393d34a0f1590834e
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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