Acetic Acid → Ethyl 4-(4-cyclopropyl-1,4-diazepan-1-yl)benzoate

HRID 16886

반응식

HRID 16886 반응식
[N:1]1([C:8]2[CH:18]=[CH:17][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(O[C:22]1(O[Si](C)(C)C)[CH2:24][CH2:23]1)C.C(O)(=O)C.C([BH3-])#N.[Na+]>O1CCCC1.CO>[CH:22]1([N:4]2[CH2:5][CH2:6][CH2:7][N:1]([C:8]3[CH:18]=[CH:17][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][CH:9]=3)[CH2:2][CH2:3]2)[CH2:24][CH2:23]1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 18425301Ethyl 4-(1,4-diazepan-1-yl)benzoate

생성물 1

HCID 66589916Ethyl 4-(4-cyclopropyl-1,4-diazepan-1-yl)benzoate수율 118%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

A solution of ethyl 4-(1,4-diazepan-1-yl)benzoate (0.621 g, 2.5 mmol), (1-ethoxycyclopropoxy)trimethylsilane (2.51 mL, 12.50 mmol) and acetic acid (0.286 mL, 5.00 mmol) in tetrahydrofuran (50 mL), methanol (5 mL) was treated with sodium cyanoborohydride (0.393 g, 6.25 mmol) at 20° C. The resulting solution was stirred at 60° C. for 18 h. The reaction mixture was cooled, filtered and evaporated to dryness. 1N HCl (40 ml) and water (60 ml) were added and the solution extracted with ethyl acetate (3×50 ml). The aqueous layer was basified to pH 10 with solid potassium carbonate and extracted with ethyl acetate (4×50 ml). The organic extracts washed with saturated NaCl (50 ml) and dried over MgSO4, filtered and evaporated to dryness. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 4-(4-cyclopropyl-1,4-diazepan-1-yl)benzoate (0.849 g, 118%) as a colourless oil.

후처리

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. customevaporated to dryness
  4. addition1N HCl (40 ml) and water (60 ml) were added
  5. extractionthe solution extracted with ethyl acetate (3×50 ml)
  6. extractionextracted with ethyl acetate (4×50 ml)
  7. washThe organic extracts washed with saturated NaCl (50 ml)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customThe crude product was purified by silica column chromatography
  12. washeluting with a gradient of 0 to 5% MeOH in DCM
  13. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-5ea8033f01d946058fca533261c3438e
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737149B2

연결된 노트

불러오는 중…