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

HRID 474724노트

반응식

HRID 474724 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[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:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:11]([F:14])([F:13])[F:12])[CH:4]=2)=[CH:26][CH:25]=1)([CH3:18])([CH3:16])[CH3:17]

참가 물질

7

반응물 4

HCID 1049PyridineHCID 8471TriethylamineHCID 27826714-Chloro-3-(trifluoromethyl)benzeneboronic acidHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

생성물 1

HCID 67774886{2-[4-(4-Chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester수율 24,157.4%

시약·촉매·용매 2

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매

실험 절차

Entire reaction was performed under dry air using syringe septa technique. 4 Å molecular sievies were added to a stirred solution of 4-chloro-3-(trifluoromethyl)phenylboronic acid (5.00 g, 0.022 mmol) and [2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert butyl ester (2.64 g, 0.051 mol, 2 eq) in dry DCM (120 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 (5.33 g, 0.010 mol, 1.3 eq), triethylamine (7.34 ml, 0.052 mol, 5 eq) and pyridine (4.25 ml, 0.052 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-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (2.21 g, yield=24%, purity=82%). [M+H]+=416.84 [M+H-56]+=360.27 1H NMR (300 MHz; CDCl3) δ/ppm 1.50 (s, 9H), 2.85 (t, J=6.97 Hz, 2H), 3.38-3.48 (m, 2H), 4.63 (br. S., 1H), 7.01 (d, J=8.57 Hz, 2H), 7.11 (dd, J=8.77, J=2.79 Hz, 1H), 7.25 (d, J=8.57 Hz, 2H), 7.36 (d, J=2.79 Hz, 1H), 7.47 (d, J=8.77 Hz, 1H)

후처리

  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

출처 및 근거

ORD 기록
ord-2cd68c8584bb41eab53bdf879c884635
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637536B2

반응 노트

불러오는 중…