Toluene → 2-Acetyl-1-benzyl-4-methoxy-6,7,8,9-tetrahydro-1h-benz[g]indole

HRID 489110Notes

Reaction equation

HRID 489110 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([O:21][CH3:22])[CH:13]=[C:14]3[CH2:20][CH2:19][CH2:18][CH2:17][C:15]3=2)[CH:10]=[C:9]1[C:23](OCC)=[O:24])C1C=CC=CC=1.[C:28]1(C)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[OH-].[Na+].O1CCC[CH2:38]1>C(OCC)C.C(=O)(O)[O-].[Na+].[CH3-].C[Al+]C.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Ti+3]>[C:23]([C:9]1[N:8]([CH2:1][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:16]2[C:11]([CH:10]=1)=[C:12]([O:21][CH3:22])[CH:13]=[C:14]1[CH2:20][CH2:19][CH2:18][CH2:17][C:15]=21)(=[O:24])[CH3:38]

Participants

8

Reactant 4

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 112106971-Benzyl-2-carboethoxy-4-methoxy-6,7,8,9-tetrahydro-1h-benz[g]indole

Product 1

HCID 114730712-Acetyl-1-benzyl-4-methoxy-6,7,8,9-tetrahydro-1h-benz[g]indoleYield 73%

Reagents, catalysts & solvents 3

HCID 53384502mu-Chlorobis(eta5-cyclopentadienyl)(dimethylaluminum)-mu-methylenetitaniumCatalystHCID 3283Diethyl EtherSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
2 °C

Procedure

To a solution of 1-benzyl-2-carboethoxy-4-methoxy-6,7,8,9-tetrahydro-1H-benz[g]indole (1.01 g, 2.77 mmol) in tetrahydrofuran (8 mL) cooled to 0° C. was added 0.5 M Tebbe Reagent in toluene (6.5 mL, 3.3 mmol). The mixture was stirred for 1 h at 2° C. then diluted with diethyl ether (32 mL) and treated with 2 N aqueous sodium hydroxide solution (2 mL) over 30 min. The mixture was diluted with excess saturated sodium bicarbonate solution and filtered through a pad of silica gel. The filtrate was concentrated in vacuo and the resulting residue triturated with 1:1 ether/hexanes. The resulting material was dissolved in 4:1 acetone/methylene chloride (5 mL) and treated with 1 N hydrochloric acid (1 mL). After standing for 20 min the mixture was diluted with saturated sodium bicarbonate solution, concentrated in vacuo, and partitioned between methylene chloride and water. The organic layer was separated, dried (sodium sulfate), filtered, and concentrated in vacuo. Purification of the residue by chromatography (silica gel, methylene chloride) provided 673 mg (73%) of the title compound as a brown film. 1H NMR (CDCl3) δ 7.49 (s, 1H), 7.15 (m, 3H), 6.78 (d, J=7 Hz, 2H), 6.24 (s, 1H), 6.11 (bs, 2H), 3.91 (s, 3H), 2.95 (m, 2H), 2.84 (m, 2H), 2.52 (s, 2H), 1.69 (m, 4H); MS ES+ m/e 334 (p+1); IR (KBr, cm−1) 3400, 2813, 1593, 1292.

Workup

  1. filtrationfiltered through a pad of silica gel
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe resulting residue triturated with 1:1 ether/hexanes
  4. dissolutionThe resulting material was dissolved in 4:1 acetone/methylene chloride (5 mL)
  5. additiontreated with 1 N hydrochloric acid (1 mL)
  6. waitAfter standing for 20 min
  7. additionthe mixture was diluted with saturated sodium bicarbonate solution
  8. concentrationconcentrated in vacuo
  9. custompartitioned between methylene chloride and water
  10. customThe organic layer was separated
  11. dry with materialdried (sodium sulfate)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customPurification of the residue by chromatography (silica gel, methylene chloride)

Sources & evidence

ORD record
ord-edf823ae0f8d4a87b69b8c97ff8ee2da
Source dataset
uspto-grants-2005_12
Patent number
US06974831B2

Reaction notes

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