Benzyl Bromide → HCID 89610365, compound

HRID 1507714Notes

Reaction equation

HRID 1507714 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[OH:18][C:19]1[C:23]([OH:24])=[C:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:21]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[C:20]=1[C:38]([O:40][CH2:41][CH3:42])=[O:39]>CCO>[CH2:1]([O:18][C:19]1[C:23]([OH:24])=[C:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:21]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[C:20]=1[C:38]([O:40][CH2:41][CH3:42])=[O:39])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7498Benzyl Bromide3×HCID 81531Diisopropylethylamine3×HCID 2801523HCID 2801523, compound

Product 1

HCID 89610365HCID 89610365, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

Benzyl bromide (2.13 ml, 17.9 mmol) was added dropwise to a suspension of DIPEA (3.12 mL, 17.9 mmol) and diethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate (UL2-001) (5 g, 14.3 mmol) in EtOH (200 mL). The reaction mixture was stirred at 50° C. for 18 h. Additional benzyl bromide (0.85 mL, 7.20 mmol) and DIPEA (1.25 mL, 7.20 mmol) were added and the reaction stirred at 60° C. for 24 h, after which further portions of benzyl bromide (0.85 ml, 7.20 mmol) and DIPEA (1.25 mL, 7.20 mmol) were added and the reaction mixture stirred at 60° C. for 24 h. The reaction mixture was allowed to cool to RT, and partitioned between EtOAc (200 mL) and sat. NaHCO3 (aq.) (200 mL), the organic layer was separated and washed with sat. NaHCO3 (aq.) (2×200 mL) dried (MgSO4), filtered and solvents removed in vacuo to give an orange oil. The residue was purified by silica gel chromatography (80 g, 0-100% EtOAc in isohexane) to afford a yellow solid. The product was recrystallised from EtOH (100 mL) to afford diethyl 3-(benzyloxy)-4-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate (23) (2.89 g, 37%) as a pale yellow solid: m/z 440 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 8.82 (s, 1H), 7.52-7.30 (m, 5H), 7.16-7.03 (m, 2H), 6.94-6.83 (m, 2H), 5.09 (s, 2H), 4.10-3.91 (m, 4H), 3.79 (s, 3H), 1.02-0.92 (m, 6H).

Workup

  1. stirringthe reaction stirred at 60° C. for 24 h
  2. stirringthe reaction mixture stirred at 60° C. for 24 h
  3. temperatureto cool to RT
  4. custompartitioned between EtOAc (200 mL) and sat. NaHCO3 (aq.) (200 mL)
  5. customthe organic layer was separated
  6. washwashed with sat. NaHCO3 (aq.) (2×200 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customsolvents removed in vacuo
  10. customto give an orange oil
  11. customThe residue was purified by silica gel chromatography (80 g, 0-100% EtOAc in isohexane)
  12. customto afford a yellow solid
  13. customThe product was recrystallised from EtOH (100 mL)

Sources & evidence

ORD record
ord-f4a9671737204f13842f337d7893d57e
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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