Hydrochloric Acid → [4-(1,3-Benzoxazol-2-yl)-2-nitrophenyl]acetonitrile

HRID 7696

반응식

HRID 7696 반응식
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][C:3]=1[N+:17]([O-:19])=[O:18].C([O-])([O-])=O.[K+].[K+].C(OC(=O)[CH2:32][C:33]#[N:34])(C)(C)C.Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>CS(C)=O.C1(C)C=CC=CC=1.O>[O:9]1[C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([CH2:32][C:33]#[N:34])=[C:3]([N+:17]([O-:19])=[O:18])[CH:4]=1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 70693tert-Butyl cyanoacetateHCID 219909702-(4-Fluoro-3-nitrophenyl)benzoxazole

생성물 1

HCID 10149379[4-(1,3-Benzoxazol-2-yl)-2-nitrophenyl]acetonitrile

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매2회HCID 1140Toluene용매

반응 조건

온도
65 °C

실험 절차

2-(4-fluoro-3-nitrophenyl)-1,3-benzoxazole (200 mg, 0.77 mmol) was dissolved in DMSO (5 mL) and K2CO3 (267 mg, 1.94 mmol) was added. The resulting yellow mixture was warmed to 65° C. and tert-butylcyanoacetate (137 mg, 0.97 mmol) was added dropwise. The dark red mixture was heated to 65° C. for 30 min, cooled to rt, and poured into H2O. The aqueous layer was acidified to pH 3 (with a 10% aqueous HCl solution) and it was extracted with EtOAc (3×). The organics were combined, washed with brine (2×), dried over Na2SO4, and evaporated to dryness. The yellow residue and p-toluenesulfonic acid (29.5 mg, 0.15 mmol) were dissolved in toluene (15 mL) and the mixture was refluxed for 20 h. After cooling to rt, the mixture was poured in H2O and the two layers were separated. The aqueous was extracted with EtOAc (3×), the organics were combined, dried over Na2SO4, and evaporated to dryness. Purification of the residue by flash chromatography on silica gel eluting with EtOAc:hexanes (3:7 to 2:3 to 1:1) afforded the desired [4-(1,3-benzoxazol-2-yl)-2-nitrophenyl]acetonitrile as an orange solid (M.p. 203° C.). 1H NMR (CDCl3, 300 MHz) δ 8.79 (s, 1H), 8.57 (dd, 1H), 7.97 (d, 1H), 7.86 (m, 2H), 7.54–7.44 (m, 2H), 4.50 (s, 2H). MS (ESI) 280 (M+H)+.

후처리

  1. temperatureThe dark red mixture was heated to 65° C. for 30 min
  2. temperaturecooled to rt
  3. extractionwas extracted with EtOAc (3×)
  4. washwashed with brine (2×)
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. temperaturethe mixture was refluxed for 20 h
  8. temperatureAfter cooling to rt
  9. customthe two layers were separated
  10. extractionThe aqueous was extracted with EtOAc (3×)
  11. dry with materialdried over Na2SO4
  12. customevaporated to dryness
  13. customPurification of the residue by flash chromatography on silica gel eluting with EtOAc:hexanes (3:7 to 2:3 to 1:1)

출처 및 근거

ORD 기록
ord-93b94594798b4f44823899c606a2d132
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087601B2

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