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

HRID 705961ノート

反応式

HRID 705961 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

実験手順

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)

後処理

  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

出典と根拠

ORDレコード
ord-2d429661e1264a0f9dbf5ebf32b13d13
出典データセット
uspto-grants-2015_11
特許番号
US09174968B2

反応ノート

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