Potassium Carbonate → HCID 9975658, compound

HRID 1033553Notes

Reaction equation

HRID 1033553 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[CH:9]3O[CH:8]3[C:7]=2[CH:15]=1)#[N:2].[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25]([O:27][CH3:28])=[O:26])=[CH:17]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[CH:9]=[C:8]([N:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]([O:27][CH3:28])=[O:26])=[CH:17]3)[C:7]=2[CH:15]=1)#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 589098Methyl indole-3-carboxylateHCID 108673602,2-Dimethyl-3,4-epoxy-6-cyanochroman

Product 1

HCID 9975658HCID 9975658, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To the solution of 6-cyano-3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-benzopyran (1.15 g, 5.71 mmol) (prepared according to Evans et al., J. Med. Chem., 1983, 26, 1582 and J. Med. Chem., 1986, 29, 2194), and indole-3-carboxylic acid, methyl ester (1.0 g, 5.71 mmol) in dimethylformamide (5.0 mL) under argon was added finely ground potassium carbonate (1.93 g, 14.0 mmol). The reaction mixture was heated at 90° C. for 4 hours and cooled to ambient temperature. It was diluted with ethyl acetate and filtered. The filtrate was washed with water, 10% citric acid, brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to yield a colorless foam. It was purified by flash chromatography (5% ethyl acetate in hexanes) to give 1-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-1H-indole-3-carboxylic acid, methyl ester (990 mg), m.p. 177°-180° C. (ether-hexanes): 1H NMR (DMSO-d6) δ 8.3 (s, 1 H), 8.21 (d, J=6.4 Hz, 1 H), 7.80 (dd, J=8.8 and 2.4 Hz, 1 H), 7.35 (m, 3 H), 7.18 (d, 8.2 Hz, 1 H), 6.90 (d, J=1.7 Hz, 1 H), 6.42 (s, 1 H), 3.93 (s, 3 H), 1.68 (s, 6 H); 13C NMR (DMSO-d6) 164.5, 156 9, 136.9, 135.5, 135.2, 130.9, 128.7, 126.7, 126.3, 123.8, 122.7, 121.4, 119.8, 118.8, 118.4, 111.6, 108.4, 103.7, 79.3, 51.3, 27.9 ppm; IR (KBr) 2224, 1705, 1207 cm-1.

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with water, 10% citric acid, brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated
  6. customto yield a colorless foam
  7. customIt was purified by flash chromatography (5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8076577e851645e381adb26ce80bc0ee
Source dataset
uspto-grants-1994_05
Patent number
US05310932

Reaction notes

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