تفاعل #657335

ord-9ea4b9af7b2f4a28ad27c315027ad250

معادلة التفاعل

CCOC(=O)COc1ccc(Br)cc1[N+](=O)[O-]
(4-bromo-2-nitro-phenoxy)-acetic acid ethyl ester
C#Cc1cccc(F)c1
1-ethynyl-3-fluorobenzene
CCN(CC)CC
triethylamine
CCOC(=O)COc1ccc(C#Cc2cccc(F)c2)cc1[N+](=O)[O-]
title compound
المردود 52.0%
CCOC(=O)COc1ccc(C#Cc2cccc(F)c2)cc1[N+](=O)[O-]
[4-(3-Fluoro-phenylethynyl)-2-nitro-phenoxy]-acetic acid ethyl ester
المردود 52.0%

المذيبات

ظروف التفاعل

درجة الحرارة
80°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىThe reaction mixture was then partitioned between ethyl acetate:heptane (1:1) and 1.0 N aqueous hydrochloric acid (100 mL each)
  2. 2
    أخرىThe organic layer was separated
  3. 3
    غسيلwashed successively with saturated aqueous sodium bicarbonate, 1:1 saturated aqueous sodium bicarbonate
  4. 4
    تجفيفsaturated aqueous ammonium chloride, saturated brine solution (100 mL each) then dried (MgSO4)
  5. 5
    ترشيحfiltered
  6. 6
    تركيزconcentrated
  7. 7
    أخرىThe product was purified
  8. 8
    غسيلthen eluted with ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 85 mL/min)

الإجراء التجريبي

To a solution of (4-bromo-2-nitro-phenoxy)-acetic acid ethyl ester (2.95 g, 9.70 mmol, 1 equiv) and 1-ethynyl-3-fluorobenzene (1.34 mL, 11.6 mmol, 1.2 equiv) in dimethylformamide (15 mL) in a microwave reactor vessel was added triethylamine (4.05 mL, 29.1 mmol, 3 equiv), copper iodide (55 mg, 0.29 mmol, 0.03 equiv) and trans-dichlorobis(tri-o-tolylphosphine) palladium(II) (152 mg, 0.19 mmol, 0.02 equiv). The reaction was placed under an argon atmosphere then heated to 80° C. in a microwave reactor for 30 min. The reaction mixture was then partitioned between ethyl acetate:heptane (1:1) and 1.0 N aqueous hydrochloric acid (100 mL each). The organic layer was separated and washed successively with saturated aqueous sodium bicarbonate, 1:1 saturated aqueous sodium bicarbonate:saturated aqueous ammonium chloride, saturated brine solution (100 mL each) then dried (MgSO4), filtered and concentrated. The product was purified using an Isco CombiFlash automated chromatography system. The residue was loaded onto a 120 g silica gel column as a solution in dichloromethane (5 mL) then eluted with ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 85 mL/min) to give 1.72 g (5.01 mmol, 52%) of the title compound as a brown oil.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US09023843B2uspto-grants-2015_05