Sodium Nitrite → Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate

HRID 385411노트

반응식

HRID 385411 반응식
N[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:18]2([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:27][CH2:28][CH:29]1[CH2:31][CH2:30]1.N([O-])=O.[Na+].CC#N.O.[ClH:40]>O.Cl[Cu]>[Cl:40][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:18]2([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19]2)=[CH:4][C:3]=1[O:27][CH2:28][CH:29]1[CH2:31][CH2:30]1

참가 물질

6

반응물 3

HCID 23668193Sodium NitriteHCID 57995480Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylateHCID 86615699Acetonitrile-hcl-water

생성물 1

HCID 57995490Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate

시약·촉매·용매 2

HCID 62652Cuprous chloride촉매HCID 962Water용매2회

반응 조건

온도
70 °C

실험 절차

Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.280 g, 0.64 mmol) was dissolved in a mixture of MeCN/H2O/HCl 10 mL/10 mL/4 mL at 0° C. A solution of NaNO2 (0.066 g, 0.96 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (0.32 g, 3.2 mmol) in water (2 mL) was added drop wise at 0° C. The reaction mixture was heated to 70° C. for 1 h and the solvent was evaporated under reduced pressure. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.110 g) as yellow oil.

후처리

  1. customthe solvent was evaporated under reduced pressure
  2. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
  3. washthe combined organic layers were washed with water (50 mL)
  4. dry with materialThe solution was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude black oil which
  8. customwas purified by chromatography over silica gel (hexane/EtOAc)

출처 및 근거

ORD 기록
ord-61f1ef60f6484010a1336901dd257006
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367863B2

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