Beta-Lapachone → HCID 178423896, compound

HRID 1159433Notes

Reaction equation

HRID 1159433 reaction equation
[CH3:1][C:2]1([CH3:18])[CH2:11][CH2:10][C:9]2[C:8](=[O:12])[C:7](=O)[C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[C:4]=2[O:3]1.[NH2:19][C:20]1[CH:48]=[CH:47][C:23]([C:24]([O:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][CH:34]2[C:46]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[C:40]3[C:35]2=[CH:36][CH:37]=[CH:38][CH:39]=3)=[O:31])=[O:25])=[CH:22][CH:21]=1.C(N(CC)CC)C>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH3:1][C:2]1([CH3:18])[CH2:11][CH2:10][C:9]2[C:8](=[O:12])/[C:7](=[N:19]\[C:20]3[CH:21]=[CH:22][C:23]([C:24]([O:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][CH:34]4[C:46]5[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=5[C:40]5[C:35]4=[CH:36][CH:37]=[CH:38][CH:39]=5)=[O:31])=[O:25])=[CH:47][CH:48]=3)/[C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[C:4]=2[O:3]1

Participants

6

Reactant 3

HCID 3885Beta-LapachoneHCID 8471TriethylamineHCID 595143802-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}ethyl 4-aminobenzoate

Product 1

HCID 178423896HCID 178423896, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalyst4×HCID 6344DichloromethaneSolvent5×

Procedure

A solution of 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (2.975 g, 12.3 mmoles) in 120 ml of methylene chloride is treated with 6.14 ml of a 1.0 M solution of TiCl4 in methylene chloride. The mixture is stirred at room temperature for 5 minutes, then a solution of 2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}ethyl 4-aminobenzoate (5.436 g, 13.5 mmoles) in 60 ml of methylene chloride is introduced followed by triethylamine (10.3 ml, 73.7 mmoles). The mixture is stirred at room temperature for 10 minutes. A second portion of 6.14 ml of a 1.0 M solution of TiCl4 in methylene chloride is added and the mixture is stirred at room temperature for 10 minutes. A third portion of 6.14 ml of a 1.0 M solution of TiCl4 in methylene chloride is added and the mixture is stirred at room temperature for 15 minutes. After stirring with the third aliquot of TiCl4, the mixture is poured onto 300 ml of ice, to form a mixture having a precipitate. The mixture is filtered to remove the precipitate and the organic and aqueous phases are then separated. The aqueous phase is extracted with two portions of 200 ml of methylene chloride. The combined organic extracts are dried with Na2SO4, filtered and concentrated in vacuo, giving a brown oil. Purification on silica gel using a gradient of 0-10% ethyl acetate in methylene chloride provided a brown reddish foam, which is triturated in diethyl ether, yielding 990 mg (13%) of the title compound as a brown solid. M.p.: 163-164° C. 400 MHz 1H NMR (DMSO-d6) δ: 8.13 (d, J=7.3 Hz, 1H), 7.93 (d, J=8.4 Hz, 2H), 7.88 (d, J=7.7 Hz, 2H), 7.82 (d, J=8.1 Hz, 1H), 7.7-7.55 (m, 5H), 7.40 (t, J=7.5 Hz, 2H), 7.30 (t, J=7.5 Hz, 2H), 6.79 (d, J=8.4 Hz, 2H), 4.33 (d, J=7.0 Hz, 2H), 4.3-4.2 (m, 3H), 3.45-3.35 (m, 2H), 2.25 (t, J=6.4 Hz, 2H), 1.79 (t, J=6.4 Hz, 2H), 1.41 (s, 6H). LCMS: 627 [M+H]. Calc. for C39H34N2O6.0.1 water: C, 74.46; H, 5.48; N, 4.46; Found C, 74.48; H, 5.06; N, 4.43.

Workup

  1. stirringThe mixture is stirred at room temperature for 10 minutes
  2. stirringthe mixture is stirred at room temperature for 10 minutes
  3. stirringthe mixture is stirred at room temperature for 15 minutes
  4. customto form a mixture
  5. filtrationThe mixture is filtered
  6. customto remove the precipitate
  7. customthe organic and aqueous phases are then separated
  8. extractionThe aqueous phase is extracted with two portions of 200 ml of methylene chloride
  9. dry with materialThe combined organic extracts are dried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customgiving a brown oil
  13. customPurification on silica gel using a gradient of 0-10% ethyl acetate in methylene chloride
  14. customprovided a brown reddish foam, which
  15. customis triturated in diethyl ether

Sources & evidence

ORD record
ord-56bb4782796e4a8b85520a68d9fca0c4
Source dataset
uspto-grants-2010_10
Patent number
US07812051B2

Reaction notes

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