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Sodium hydride → 2-((3-cyclohexyl-6-(methoxycarbonyl)-2-(2-vinylphenyl)-1H-indol-1-yl)methyl)acrylic acid

HRID 860709
Notes
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Reaction equation

HRID 860709 reaction equation
[H-].[Na+].[CH:3]1([C:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][CH:16]=3)[NH:11][C:10]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH:28]=[CH2:29])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[H][H].Br[CH2:33][C:34](=[CH2:38])[C:35]([OH:37])=[O:36]>C1COCC1.CN(C=O)C>[CH:3]1([C:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][CH:16]=3)[N:11]([CH2:38][C:34](=[CH2:33])[C:35]([OH:37])=[O:36])[C:10]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH:28]=[CH2:29])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 5588842-(Bromomethyl)propenoic acidHCID 58765232methyl 3-cyclohexyl-2-(2-vinylphenyl)1H-indole-6-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 692042162-((3-cyclohexyl-6-(methoxycarbonyl)-2-(2-vinylphenyl)-1H-indol-1-yl)methyl)acrylic acidYield 45.9%

Reagents, catalysts & solvents

2
HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (155 mg of a 95% dispersion in mineral oil, 6.13 mmol) was added in portions during 5 min to a stirred and cooled solution (ice-water bath) of 7 (1.0 g, 2.79 mmol) in THF (7 mL). When the evolution of hydrogen subsided DMF (2 mL) was added followed by a solution of bromomethylacrylic acid (505 mg, 3.06 mmol) in THF (1.5 mL). Stirring was continued with cooling (10 min) and then at 22° C. for 30 min. The mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic layer was washed (water, brine), dried (sodium sulfate) and concentrated. The residue was chromatographed on silicic acid (15 g) using the flash technique and eluting with methylene chloride:ethyl acetate:acetic acid (10:1:0.005). The product containing fraction was concentrated on a rotary evaporator to leave 2-((3-cyclohexyl-6-(methoxycarbonyl)-2-(2-vinylphenyl)-1H-indol-1-yl)methyl)acrylic acid (568 mg, 40%) as a yellow gum. A sample (142 mg) was further purified on a Shimadzu preparatory liquid chromatograph. The fraction containing the product was concentrated to leave 13 (R=H) as a granular solid. ESI-MS m/z 433 (MH+), 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.07–1.37 (m, 3 H) 1.58–1.88 (m, 7 H) 2.41–2.53 (m, 1 H) 3.93 (s, 3 H) 4.50 (d, J=18.31 Hz, 1 H) 4.84 (d, J=18.31 Hz, 1 H) 4.89 (s, 1 H) 5.13 (d, J=10.99 Hz, 1 H) 5.29 (s, 1 H) 5.68 (d, J=17.70 Hz, 1 H) 6.19 (s, 1 H) 6.36 (dd, J=17.55, 11.14 Hz, 1 H) 7.15 (d, J=7.63 Hz, 1 H) 7.31 (t, J=7.48 Hz, 1 H) 7.45 (t, J=7.63 Hz, 1 H) 7.70 (d, J=7.93 Hz, 1 H) 7.76–7.87 (m, 2 H) 7.96 (s, 1 H).

Workup

  1. additionwas added
  2. stirringStirring
  3. temperaturewith cooling (10 min)
  4. concentrationThe mixture was concentrated
  5. customthe residue partitioned between ethyl acetate and water
  6. washThe organic layer was washed (water, brine)
  7. dry with materialdried (sodium sulfate)
  8. concentrationconcentrated
  9. customThe residue was chromatographed on silicic acid (15 g)
  10. washeluting with methylene chloride:ethyl acetate:acetic acid (10:1:0.005)
  11. additionThe product containing fraction
  12. concentrationwas concentrated on a rotary evaporator

Sources & evidence

ORD record
ord-7b50a714a73f4752b40249e9cadecaf1
Source dataset
uspto-grants-2006_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07153848B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes