Sodium Carbonate → methyl 2-(2-acetylphenyl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1394870Notes

Reaction equation

HRID 1394870 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[CH:7]1([C:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]([O:24][CH3:25])=[O:23])=[CH:19][CH:20]=3)[NH:15][C:14]=2B2OC(C)(C)C(C)(C)O2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.Br[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:42](=[O:44])[CH3:43].[Li+].[Cl-]>C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:42]([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[C:14]1[NH:15][C:16]2[C:21]([C:13]=1[CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1)=[CH:20][CH:19]=[C:18]([C:22]([O:24][CH3:25])=[O:23])[CH:17]=2)(=[O:44])[CH3:43]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 750602'-BromoacetophenoneHCID 433294Lithium ChlorideHCID 23152432methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate

Product 1

HCID 58765163methyl 2-(2-acetylphenyl)-3-cyclohexyl-1H-indole-6-carboxylateYield 91%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A 2M aqueous solution of Na2CO3 (2.5 mL, 5.0 mmol) was added to a mixture of; methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate (766 mg, 2.0 mmol), 2′-bromoacetophenone (478 mg, 2.4 mmol) and LiCl (170 mg, 4.0 mmol), in ethanol (5 mL) and toluene (5 mL). The mixture was then degassed by sequentially applying vacuum followed by flushing with N2. Pd(PPh3)4 (115 mg, 0.1 mmol) was then added and the reaction heated at 80° C. for 4 hr. The reaction mixture was then filtered and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography using hexanes to 20% ethyl acetate in hexanes as eluent to give the title compound as a white foam which could be crushed to a powder, (686 mg, 91% yield). MS m/z 374(M−H−); 1H NMR (500 MHz, CD3OD) δ ppm 1.30 (m, 1 H) 1.41-1.64 (m, 3H) 1.82-2.21 (m, 9 H) 3.26 (m, 1 H) 3.95 (s, 3 H) 7.40 (m, 1 H) 7.49 (m, 1 H) 7.61 (m, 1H) 7.69 (m, 1 H) 7.79 (m, 1 H) 7.84 (m, 1 H) 8.29 (s, 1 H).

Workup

  1. customThe mixture was then degassed
  2. customby flushing with N2
  3. filtrationThe reaction mixture was then filtered
  4. concentrationconcentrated under reduced pressure
  5. customThe resultant residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-5e23cd6bffc14a8aac63a13c0c2b42b6
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

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