Beta-Lapachone → HCID 58601388, compound

HRID 1914989Notes

Reaction equation

HRID 1914989 reaction equation
[CH3:1][C:2]1([CH3:18])[CH2:11][CH2:10][C:9]2[C:8](=[O:12])[C:7](=[O:13])[C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[C:4]=2[O:3]1.[O-]S(S([O-])=O)=O.[Na+].[Na+].[C:27]([O:31][C:32]([NH:34][C:35]([CH3:40])([C:37]([OH:39])=O)[CH3:36])=[O:33])([CH3:30])([CH3:29])[CH3:28].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:72](OC(=O)C)(=[O:74])[CH3:73]>[Zn].CN(C=O)C>[C:27]([O:31][C:32]([NH:34][C:35]([CH3:36])([C:37]([O:13][C:7]1[C:8]([O:12][C:72](=[O:74])[CH3:73])=[C:9]2[C:4](=[C:5]3[CH:17]=[CH:16][CH:15]=[CH:14][C:6]=13)[O:3][C:2]([CH3:18])([CH3:1])[CH2:11][CH2:10]2)=[O:39])[CH3:40])=[O:33])([CH3:28])([CH3:29])[CH3:30]

Participants

9

Reactant 6

HCID 3885Beta-LapachoneHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 24489Sodium DithioniteHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanine

Product 1

HCID 58601388HCID 58601388, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

The compound 5-(acetyloxy)-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromen-6-yl N-(tert-butoxycarbonyl)-2-methylalaninate (27) is synthesized as described in scheme 1a using zinc dust (2.0 g, 30.5 mmol), 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (2.0 g, 8.26 mmol), Na2S2O4 (5.75 g, 33.0 mmol), N-(tert-butoxycarbonyl)-2-methylalanine (3.36 g, 16.51 mmol), triethylamine (1.04 mL, 7.43 mmol), HBTU (6.26 g, 16.5 mmol) and DMF (30 mL) for the 1st step. The acetylation step is carried out using zinc dust (1.0 g, 15.3 mmol), thriethylamine (1.04 mL, 7.43 mmol) and acetic anhydride (20 mL). Both the compounds are generated in the reaction. The crude mixture is purified by two consecutive flash column chromatography (SiO2, 1st using a gradient from 100% dichloromethane to 2% EtOAc in dichloromethane and 2nd using a gradient from 10% EtOAc in hexanes to 25% EtOAc in hexanes) to afford pure desired single isomer product (0.405 g, %) as a white solid. 400 MHz 1H NMR (CDCl3) δ: 8.19 (d, J=8.8 Hz, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.50-7.35 (m, 2H), 5.19 (br. s, 1H), 2.67 (t, J=6.6 Hz, 2H), 2.37 (s, 3H), 1.87 (t, J=6.8 Hz, 2H), 1.78 (s, 6H), 1.47 (s, 9H), 1.42 (s, 6H); LCMS: 472 [M+H].

Workup

  1. customBoth the compounds are generated in the reaction
  2. customThe crude mixture is purified by two consecutive flash column chromatography (SiO2
  3. customto afford pure desired single isomer product (0.405 g, %) as a white solid

Sources & evidence

ORD record
ord-2240a99050f24a5e920a30d4349e69f8
Source dataset
uspto-grants-2013_12
Patent number
US08614228B2

Reaction notes

Loading…