Water → methyl 3-(t-butyloxycarbonyl)-1-hydroxymethyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate

HRID 366835Notes

Reaction equation

HRID 366835 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:19]2[C:11](=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14]([C:20]([O:22][CH3:23])=[O:21])=[CH:13]3)[CH:10]([CH2:24][O:25]N2C(C)(C)CCCC2(C)C)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O>C1COCC1.CC(O)=O.[Zn]>[C:1]([O:5][C:6]([N:8]1[C:19]2[C:11](=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14]([C:20]([O:22][CH3:23])=[O:21])=[CH:13]3)[CH:10]([CH2:24][OH:25])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 962WaterHCID 10791080methyl 3-(t-butyloxycarbonyl)-1-[(2,2,6,6-tetramethylpiperidino)oxy]methyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate

Product 1

HCID 10569587methyl 3-(t-butyloxycarbonyl)-1-hydroxymethyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylateYield 79%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Zinc powder (7.39 g, 113 mmol) was added to a solution of 54 (6.86 g, 14.1 mmol) in THF (150 mL), HOAc (150 mL), and H2O (50 mL). The mixture was stirred at reflux for 40 min, cooled, and filtered through Celite eluting with EtOAc. The filtrate was evaporated and the residue diluted with H2O and extracted with EtOAc (×2). The extracts were washed with H2O, aq NaHCO3, and dried (Na2SO4) and evaporated. Recrystallization from MeOH gave methyl 3-(t-butyloxycarbonyl)-1-hydroxymethyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate (55) as a white solid (3.86 g, 79%), mp 189.5-191° C. (dec.). The mother liquor was purified by chromatography (40% EtOAc-petroleum ether) to give more alcohol (0.74 g, 15%). 1H NMR [(CD3)2SO] δ 11.88 (s, 1 H, NH), 7.87 (v br s, 1 H, H-4), 7.29 (d, J=8.9 Hz, 1 H, H-5), 7.11 (d, J=1.4 Hz, 1 H , H-8), 4.95 (t, J=5.2 Hz, 1 H, OH), 4.03 (t, J=10.5 Hz, 1 H), 3.92-3.86 (m, 1 H), 3.87 (s, 3 H, CO2Me), 3.82-3.75 (m, 1 H), 3.67 (br s, 1 H), 3.55-3.48 (m, 1 H), 1.51 (s, 9 H, t-Bu); 13C NMR δ 161.6, 151.8, 136.2, 134.6, 127.8, 123.7, 122.6, 113.3, 113.3, 111.3, 105.5, 79.3, 63.1, 51.7, 51.2, 42.2, 28.1. Anal. Calculated for C18H22N2O5 : C, 62.4; H, 6.4; N, 8.1. Found: C, 62.3; H, 6.6; N, 8.3%.

Workup

  1. temperatureat reflux for 40 min
  2. temperaturecooled
  3. filtrationfiltered through Celite
  4. washeluting with EtOAc
  5. customThe filtrate was evaporated
  6. additionthe residue diluted with H2O
  7. extractionextracted with EtOAc (×2)
  8. washThe extracts were washed with H2O, aq NaHCO3
  9. dry with materialdried (Na2SO4)
  10. customevaporated
  11. customRecrystallization from MeOH

Sources & evidence

ORD record
ord-8fbdbac26cbb4c9a85248fb78bf634d9
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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