Trifluoroacetic acid → Methyl 3-cyclohexyl-1H-indole-6-carboxylate

HRID 1453345Notes

Reaction equation

HRID 1453345 reaction equation
[C:1]1(=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=2)[CH:10]=[CH:9]1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[CH:1]1([C:10]2[C:11]3[C:16](=[CH:15][C:14]([C:17]([O:19][CH3:20])=[O:18])=[CH:13][CH:12]=3)[NH:8][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7967CyclohexanoneHCID 12052TriethylsilaneHCID 639844Methyl indole-6-carboxylate

Product 1

HCID 11230631Methyl 3-cyclohexyl-1H-indole-6-carboxylateYield 85.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
10 °C

Procedure

Cyclohexanone (42.46 mL, 0.40 mol) was added in a single portion to a stirred solution of methyl indole-6-carboxylate (47.8 g, 0.27 m) in dry dichloromethane (500 mL). The reaction mixture was then cooled to 10° C. and trifluoroacetic acid (63.13 mL, 0.8 m) was added dropwise followed by triethyl silane (174.5 mL, 1.09 m). Upon addition, the temperature was allowed to rise to rt, after which it was stirred for a further 12 h. Dichloromethane (200 mL) was then added and the reaction mixture was washed successively with with 10% sodium bicarbonate solution and brine. The organic layer dried over sodium sulfate, filtered and concentrated under vacuum. The resultant residuce was purified by flash chromatography on silica (60-120) using hexane-ethyl acetate (9.5:0.5) mixture as eluant. Homogeneous fractions were combined and evaporated to give 60 g of the desired product (85%). Analytical data on this material was consistant with that observed with a sample prepared by the alternative route described above.

Workup

  1. additionUpon addition
  2. customto rise to rt
  3. washthe reaction mixture was washed successively with with 10% sodium bicarbonate solution and brine
  4. dry with materialThe organic layer dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe resultant residuce was purified by flash chromatography on silica (60-120)
  8. customevaporated

Sources & evidence

ORD record
ord-14a575fe1f124f3fa5a4e81c3c367b20
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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