Dimethylformamide → 5-Formyl-2-methyl-1-t-butyloxycarbonylindole

HRID 856997Notes

Reaction equation

HRID 856997 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]([CH3:18])=[CH:5]2.CN([CH:22]=[O:23])C.C([Li])(C)(C)C.CCCCCCC>C1COCC1.CCOC(C)=O.CC(O)=O>[CH:22]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]([CH3:18])=[CH:5]2)=[O:23]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8900HeptaneHCID 218654515-Bromo-2-methyl-1-t-butyloxycarbonylindoleHCID 178418306HCID 178418306, compound

Product 1

HCID 218654945-Formyl-2-methyl-1-t-butyloxycarbonylindoleYield 6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-methyl-1-t-butyloxycarbonylindole (1.55 g, 5.0 mmol) and DMF (0.39 mL, 5.0 mmol) in anhydrous THF (15 mL) was cooled with stirring to −78° C. A solution of t-butyl lithium in heptane (1.7M, 7.35 mL, 12.5 mmol) was added dropwise over 5 min. The reaction mixture was then stirred for 1 h. HOAc (1 mL) was added and the reaction mixture was diluted with EtOAc (50 mL). The organic mix was washed three times with a 10% KHSO4 solution (10 mL), once with a saturated NaHCO3 solution and once with brine. The organic solution was dried over MgSO4, filtered and concentrated in vacuo. Column chromatography (EtOAc:hexane::95:5) afforded three products after removal of solvent in vacuo: (1) 1,5-di-(t-butyloxycarbonyl)-2-methylindole, an oil (89 mg, 6% yield, Rf=0.8): 1H NMR (CDCl3, 300 MHz): 8.10 (d, 1H, J=8), 8.09 (s, 1H), 7.87 (d, 1H, J=8), 6.37 (s, 1H), 2.60 (s, 3H), 1.69 (s, 9H), 1.62 (s, 9H); (2) the title product, a light orange solid (726 mg, 56% yield, Rf=0.5): 1H NMR (CDCl3, 300 MHz): 10.0 (s, 1H0, 8.24 (d, 1H, J=8), 7.97 (d, 1H, J=2), 7.77 (dd, 1H, J=8, 2), 6.44 (s, 1H), 2.62 (d, 3H, J=1), 1.70 (s, 9H); (3) 5-formyl-2-methylindole, a light orange solid (139 mg, 17% yield, Rf=0.3): 1H NMR (CDCl3, 300 MHz): 10.0 (s, 1H), 8.20 (br s, 1H), 7.71 (d, 1H, J=1), 7.68 (d, 1H, J=8), 7.37 (d, 1H, J=8), 6.37 (t, 1H, J=1), 2.48 (d, 3H, J=1); MS (ES+): 160 (C10H10NO, M++H).

Workup

  1. stirringThe reaction mixture was then stirred for 1 h
  2. additionThe organic mix
  3. washwas washed three times with a 10% KHSO4 solution (10 mL)
  4. dry with materialThe organic solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customColumn chromatography (EtOAc:hexane::95:5) afforded three products
  8. customafter removal of solvent in vacuo

Sources & evidence

ORD record
ord-16c25a8fcb5d434ab1ada69bca48f750
Source dataset
uspto-grants-2006_12
Patent number
US07144894B2

Reaction notes

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