Acetic Acid → Methyl 5-{butyl[4-(phenylethynyl)benzyl]amino}-2-fluorobenzoate

HRID 551965노트

반응식

HRID 551965 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:13]1([C:19]#[C:20][C:21]2[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O)(=O)C.[CH:33](=O)[CH2:34][CH2:35][CH3:36].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1.O>[CH2:33]([N:1]([CH2:25][C:24]1[CH:27]=[CH:28][C:21]([C:20]#[C:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:22][CH:23]=1)[C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])[CH2:34][CH2:35][CH3:36]

참가 물질

8

반응물 5

HCID 176Acetic Acid2회HCID 261ButanalHCID 6099084-(Phenylethynyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydride2회HCID 15621043Methyl 5-amino-2-fluorobenzoate

생성물 1

HCID 57554483Methyl 5-{butyl[4-(phenylethynyl)benzyl]amino}-2-fluorobenzoate수율 75.1%

시약·촉매·용매 2

HCID 962Water용매2회HCID 1140Toluene용매

반응 조건

온도
70 °C

실험 절차

A solution of methyl 5-amino-2-fluorobenzoate (500 mg, 2.96 mmol), 4-(phenylethynyl)benzaldehyde (6 10 mg, 2.96 mmol) and acetic acid (0.25 mL, 4.40 mmol) in toluene (20 mL) was heated under reflux for 3 h with azeotropic removal of water. Then the solvent was removed by distillation at atmospheric pressure and replaced by anhydrous DCE (20 mL). Butanal (Fluka, 0.66 mL, 7.39 mmol), sodium triacetoxyborohydride (1880 mg, 8.87 mmol) and acetic acid (0.25 mL, 4.40 mmol) were added and the resulting mixture was heated at 70° C. After 45 min, an additional amount of sodium triacetoxyborohydride (630 mg, 2.96 mmol) was added. After 45 min, the reaction mixture was diluted with water (40 mL) and extracted with DCM (3×20 mL). The combined organic layers were dried over MgSO4 and the solvents were removed under reduced pressure. Purification by flash chromatography on silicagel (cHex/EtOAc): gave. 924 mg (75%) of the title compound as a colorless oil. HPLC, Rt: 5.6 min (purity: 99.8%). LC/MS, M+(ESI): 416.1. 1H NMR (CDCl3) δ: 7.51-7.44 (m, 4H), 7.32 (m, 3H), 7.17 (m, 3H), 6.92 (dd, J=9.8, 9.7 Hz, 1H), 6.73 (m, 1H), 4.49 (s, 2H), 3.88 (s, 3H), 3.36 (t, J=7.2 Hz, 2H), 1.60 (m, 2H), 1.34 (m, 2H), 0.93 (t, J=7.2 Hz, 3H).

후처리

  1. customThen the solvent was removed by distillation at atmospheric pressure
  2. waitAfter 45 min
  3. extractionextracted with DCM (3×20 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. customthe solvents were removed under reduced pressure
  6. customPurification by flash chromatography on silicagel (cHex/EtOAc)
  7. customgave

출처 및 근거

ORD 기록
ord-1070f5b0b7db4b6598ffb3e68c69fe06
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947851B2

반응 노트

불러오는 중…