Ethyl Acetate → Ethyl 6-chloro-5-methyl-1h-indole-2-carboxylate

HRID 857450Notes

Reaction equation

HRID 857450 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](OCC)=O)=[C:4]([N+:14]([O-])=O)[C:3]=1C.[K].[C:19](=O)([O-])O.[Na+].[C:24]([O:27][CH2:28][CH3:29])(=[O:26])C>C(O)(=O)C.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([CH:8]=[C:9]([C:24]([O:27][CH2:28][CH3:29])=[O:26])[NH:14]2)=[CH:6][C:7]=1[CH3:19]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium Bicarbonate2×HCID 5462222PotassiumHCID 21868719Ethyl 4-chloro-3-methyl-2-nitrophenylacetate

Product 1

HCID 21868716Ethyl 6-chloro-5-methyl-1h-indole-2-carboxylateYield 14%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

Iron powder (3.34 g, 60 mmol) was added in 1 portion to a stirred solution of ethyl 4-chloro-3-methyl-2-nitrophenylacetate, potassium salt (6.5 g, 20 mmol) in acetic acid (60 mL) at room temperature under Ar. The reaction was then heated to 90° C. and stirred for 1 h. After allowing to cool to room temperature the mixture was cautiously poured into saturated aqueous sodium hydrogen carbonate solution (200 mL) containing solid sodium hydrogen carbonate (10 g) and ethyl acetate (200 mL). The mixture was filtered through celite and the aqueous and organic layers were separated. The aqueous layer was extracted with ethyl acetate (2×200 mL) and the combined organic extracts were washed with brine (1×200 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude solid. The solid was adsorbed onto sodium sulfate (10 g) and purified by flash column chromatography [SiO2; ethyl acetate-heptane (1:5)→(1:0)] to give the product as yellow solid (1.6 g, 14% over 2 steps). IR νmax (Nujol)/cm−1 3319, 2925, 2855, 1683, 1623, 1570, 1530, 1555, 1418, 1368, 1339, 1330, 1280, 1241, 1158, 1120, 1107, 1021, 996, 976, 885, 855, 828, 773, 736, 664, 580, 574, 514 and 489; NMR δH (400 MHz; CDCl3) 8.82 (1H, br. s), 7.52 (1H, s), 7.44 (1H, s), 7.12 (1H, m), 4.39 (2H, q, J 7.1 Hz), 2.45 (3H, s), 1.40 (3H, t, J 7.1 Hz).

Workup

  1. temperatureto cool to room temperature the mixture
  2. filtrationThe mixture was filtered through celite
  3. customthe aqueous and organic layers were separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
  5. washthe combined organic extracts were washed with brine (1×200 mL)
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customthe solvent removed under vacuum
  9. customto leave a crude solid
  10. custompurified by flash column chromatography [SiO2; ethyl acetate-heptane (1:5)→(1:0)]

Sources & evidence

ORD record
ord-b0d70665ebfd49b09e19fa55696b2148
Source dataset
uspto-grants-2006_12
Patent number
US07145009B2

Reaction notes

Loading…