Hydrogen Bromide → HCID 117642820, compound

HRID 1507756Notes

Reaction equation

HRID 1507756 reaction equation
Br.C([O:9][C:10]1[C:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:13]([C:23](=[O:27])[N:24]([CH3:26])[CH3:25])[N:12]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[C:11]=1[C:36]([O:38][CH2:39][CH3:40])=[O:37])C1C=CC=CC=1>CC(O)=O.C(Cl)Cl>[CH2:16]([O:15][C:14]1[C:10]([OH:9])=[C:11]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[N:12]([C:28]2[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=2)[C:13]=1[C:23](=[O:27])[N:24]([CH3:26])[CH3:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 2

HCID 260Hydrogen Bromide2×HCID 89610459HCID 89610459, compound

Product 1

HCID 117642820HCID 117642820, compoundYield 63.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

HBr (33% in AcOH, 970 μL, 5.34 mmol) was added to a stirred solution of ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (6) (2.82 g, 5.34 mmol) in AcOH (40 mL) and the reaction was allowed to stir for 16 h at RT. The reaction mixture was diluted with DCM (100 mL), washed with water (100 mL), brine (2×100 mL), the organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was redissolved in AcOH (40 mL) and HBr (33% in AcOH, 970 μL, 5.34 mmol) was added dropwise and the reaction was allowed to stir at RT for 40 h. The reaction mixture was diluted with DCM (100 mL), washed with water (100 mL) and brine (2×100 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (40 g, 0-30% EtOAc in toluene) to afford ethyl 4-(benzyloxy)-5-(dimethylcarbamoyl)-3-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (60) (1.48 g, 57%) as a colourless oil: m/z 439 (M+H)+ (ES+); 437 (M−H)− (ES−). 1H NMR (400 MHz, DMSO-d6) δ: 8.75 (s, 1H), 7.42-7.28 (m, 5H), 7.12-7.05 (m, 2H), 6.91-6.84 (m, 2H), 5.01 (s, 2H), 4.02 (q, J=7.1 Hz, 2H), 3.76 (s, 3H), 2.68 (s, 3H), 2.66 (s, 3H), 1.0 (t, J=7.1 Hz, 3H).

Workup

  1. washwashed with water (100 mL), brine (2×100 mL)
  2. dry with materialthe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in AcOH (40 mL)
  6. stirringto stir at RT for 40 h
  7. washwashed with water (100 mL) and brine (2×100 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel chromatography (40 g, 0-30% EtOAc in toluene)

Sources & evidence

ORD record
ord-5a1d38e4ab8247938a324fb45588c6b6
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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