Tributylamine → 3-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid ethyl ester

HRID 889566노트

반응식

HRID 889566 반응식
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N:13]2[CH:17]=[N:16][N:15]=[N:14]2)=[C:6]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])[CH:7]=1.[CH2:18](OC(OCC)C=C)[CH3:19].N(CCCC)(CCCC)CCCC>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([O:11][C:10](=[O:12])[CH2:9][CH2:8][C:6]1[CH:7]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]=1[N:13]1[CH:17]=[N:16][N:15]=[N:14]1)[CH3:19]

참가 물질

7

반응물 3

HCID 7622TributylamineHCID 624773,3-Diethoxy-1-propeneHCID 669388573-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid

생성물 1

HCID 669383413-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid ethyl ester수율 66.8%

시약·촉매·용매 3

HCID 70681Tetrabutylammonium Chloride촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

3-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid: To a mixture of 117A (956 mg, 4.00 mmol), 3,3-diethoxyprop-1-ene (1562 mg, 12.00 mmol), and Bu4NCl (1110 mg, 4.00 mmol) in DMF (22 mL) was added Bu3N (1480 mg, 8.00 mmol). To this mixture under N2 was added Pd(OAc)2 (26.9 mg, 0.12 mmol). The resulting mixture was stirred at 90° C. for 1.5 h, then cooled to rt and quenched with 2N HCl (10 mL). The resulting mixture was stirred for 20 min, then evaporated. The mixture was diluted with EtOAc, washed with water and brine, dried over MgSO4, and purified by flash chromatography to provide 3-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid ethyl ester (695 mg, 66.8%). LCMS m/z 261.2 (M+H)+. To a solution of this intermediate (690 mg, 2.65 mmol), in THF (10 mL) was added 2N LiOH (10 mL). The resulting mixture was stirred at rt for 3 h, then acidified to pH 3-4 with 2N HCl at 0° C. The mixture was concentrated and extracted with EtOAc (5×20 mL). The combined organic layers were washed with brine, dried over MgSO4, and purified by prep. HPLC to give 117B (567 mg, 92%). LCMS m/z 233.2 (M+H)+.

후처리

  1. temperaturecooled to rt
  2. customquenched with 2N HCl (10 mL)
  3. stirringThe resulting mixture was stirred for 20 min
  4. customevaporated
  5. additionThe mixture was diluted with EtOAc
  6. washwashed with water and brine
  7. dry with materialdried over MgSO4
  8. custompurified by flash chromatography

출처 및 근거

ORD 기록
ord-6fb84f37688549b48cd5799e5df8c943
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08252830B2

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