Borane;tetrahydrofuran → HCID 18929236, compound

HRID 1599827Notes

Reaction equation

HRID 1599827 reaction equation
B.C1COCC1.[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]([NH:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([OH:23])=[O:22])=O>C1COCC1>[C:21]([C:20]1[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=1[NH:18][CH2:16][CH2:15][NH:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[F:7])([OH:23])=[O:22]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 10684750HCID 10684750, compound

Product 1

HCID 18929236HCID 18929236, compoundYield 24.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of BH3.THF (1.00M, 10.0 mL 300 mol %) at 5° C. was added a solution of 2-(2-(((2-fluorophenyl)amino)acetylamino)benzoic acid from Example 2 (1.0 g, 3.47 mmol) in anhydrous THF (10 mL). After stirring for 5 min at 10° C., the reaction mixture was refluxed for 2.5 h and then cooled to rt. The reaction mixture was quenched with 25% (w/v) NaOH (4 mL) and then the solution was refluxed for 4 h. After cooling to rt, the reaction mixture was stirred for 20 h, water (50 mL) was added, and then the mixture was extracted with ether (3×100 mL). The water layer was acidified with 1N HCl to pH=3-4 and then the light crystalline product which crystallized was filtered and washed several times with cold water. After drying in a vacuum oven at 50° C. for 5 h, 0.23 g (24%) of the title compound was obtained which contained ca 5% of an impurity by 1H NMR: mp 127°-128° C. Further purification by LPLC (EtOAc-hexane 1:2), afforded, after drying in vacuo, 176 mg (19%) of the title compound: mp 135.7°-136.2° C.; 1H NMR (CDCl3) δ8.00 (d, 1H, J=8, NH), 7.42 (t, 2H, J=6.8), 7.05-6.97 (m, 2H), 6.80-6.65 (m, 4H), 3.55 (d, 2H, J=4.8), 3.51 (d, 2H, J=4); 13C NMR (CDCl3) δ173.37, 151.72 (d, J=238), 151.38, 135.63, 132.83, 124.60 (d, J=3.8), 117.27 (d, J=6.8), 115.30, 114.73, 114.54, 112.32, 111.33, 109.25, 42.75, 42.12; MS (EI, m/z) 274 (M+).

Workup

  1. temperaturethe reaction mixture was refluxed for 2.5 h
  2. temperaturecooled to rt
  3. customThe reaction mixture was quenched with 25% (w/v) NaOH (4 mL)
  4. temperaturethe solution was refluxed for 4 h
  5. temperatureAfter cooling to rt
  6. stirringthe reaction mixture was stirred for 20 h
  7. additionwater (50 mL) was added
  8. extractionthe mixture was extracted with ether (3×100 mL)
  9. customthe light crystalline product which crystallized
  10. filtrationwas filtered
  11. washwashed several times with cold water
  12. customAfter drying in a vacuum oven at 50° C. for 5 h

Sources & evidence

ORD record
ord-aa8064daf294411f8edf86bd921fd1ab
Source dataset
uspto-grants-1998_04
Patent number
US05741926

Reaction notes

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