Diethyl Oxalate → diisopropyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate

HRID 1507712노트

반응식

HRID 1507712 반응식
CC(C)[O-].[Li+].[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]([CH2:22][C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])=[CH:10][CH:9]=1.BrCC(OC(C)C)=O.[C:37](OCC)(=[O:43])[C:38](OCC)=[O:39]>>[OH:39][C:38]1[C:37]([OH:43])=[C:22]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[N:14]([C:11]2[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[CH:13][CH:12]=2)[C:15]=1[C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17]

참가 물질

5

반응물 4

HCID 7268Diethyl OxalateHCID 121593Isopropyl bromoacetateHCID 23673350Lithium propan-2-olate2회HCID 89610362Diisopropyl 2,2'-((4-methoxyphenyl)azanediyl)diacetate

생성물 1

HCID 71599119diisopropyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate수율 1%

반응 조건

온도
65 °C

실험 절차

Lithium isopropoxide (2M in THF) (10.4 mL, 20.8 mmol) was added to a mixture of diisopropyl 2,2′-((4-methoxyphenyl)azanediyl)diacetate (21) (2.69 g, 8.32 mmol) [prepared using the same procedure as Example B step (i) using isopropyl 2-bromoacetate] and diethyl oxalate (1.13 mL, 8.32 mmol), the mixture was stirred at 65° C. for 16 h. A further portion of lithium isopropoxide (2M in THF) (5.2 ml, 10.4 mmol) was added and the reaction stirred at 65° C. for 3 h. The reaction was quenched with acetic acid (5 mL) and the volatiles removed in vacuo, the crude product was took up in EtOAc (100 mL) and partitioned with water (100 mL), the aqueous was washed with EtOAc (2×100 mL) combined organics were washed with brine (150 mL), dried (MgSO4), filtered and solvents removed in vacuo to afford a brown oil. The crude product was recrystallised from hot i-PrOH (50 mL), to provide a white solid. The solid was purified by silica gel chromatography (12 g, 0-50% EtOAc in isohexane) to afford diisopropyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate (UL2-020) (21 mg, 1%) as a white solid: m/z 378 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 8.62 (s, 2H), 7.12-7.01 (m, 2H), 6.93-6.84 (m, 2H), 4.80 (sept., J=6.3 Hz, 2H), 3.78 (s, 3H), 0.95 (d, J=6.2 Hz, 12H).

후처리

  1. customprepared
  2. stirringthe reaction stirred at 65° C. for 3 h
  3. customThe reaction was quenched with acetic acid (5 mL)
  4. customthe volatiles removed in vacuo
  5. custompartitioned with water (100 mL)
  6. washthe aqueous was washed with EtOAc (2×100 mL)
  7. washcombined organics were washed with brine (150 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customsolvents removed in vacuo
  11. customto afford a brown oil
  12. customThe crude product was recrystallised from hot i-PrOH (50 mL)
  13. customto provide a white solid
  14. customThe solid was purified by silica gel chromatography (12 g, 0-50% EtOAc in isohexane)

출처 및 근거

ORD 기록
ord-d44282c0f42f4706b11e58edeb9402b1
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221756B2

반응 노트

불러오는 중…