Sodium Carbonate → Methyl 2-(2-(benzyloxy)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1394866Notes

Reaction equation

HRID 1394866 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.[CH2:35]([O:42][C:43]1[C:48](Br)=[CH:47][CH:46]=[CH:45][N:44]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[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>[CH2:35]([O:42][C:43]1[C:48]([C:14]2[NH:15][C:16]3[C:21]([C:13]=2[CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)=[CH:20][CH:19]=[C:18]([C:22]([O:24][CH3:25])=[O:23])[CH:17]=3)=[CH:47][CH:46]=[CH:45][N:44]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 147124562-Benzyloxy-3-bromopyridineHCID 23152432methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate

Product 1

HCID 58765212Methyl 2-(2-(benzyloxy)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylateYield 70.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

2M Na2CO3 (1.25 mL, 2.5 mmol) aqueous solution was added to a suspension of methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate (383 mg, 1.0 mmol), 2-(benzyloxy)-3-bromopyridine (317 mg, 1.2 mmol) and LiCl (84.8 mg, 2.0 mmol), in ethanol (3 mL) and toluene (3 mL). The mixture was degassed by evacuating the reaction flask and then flushing with N2. Pd(PPh3)4 (58 mg, 0.05 mmol) was then added, and the reaction mixture was heated at 80° C. for 6 hr. The reaction mixture was then filtered and concentrated in vacuo, and the resultant residue was purified by silica gel flash chromotagraphy using hexanes to 50% ethyl acetate in hexanes as eluent to afford the title compound as a yellowish solid, (310 mg, 70% yield). MS m/z 441(MH+); 1H NMR (500 MHz, CDCl3) δ ppm 1.32-1.46 (m, 3 H) 1.78-1.93 (m, 5 H) 2.05-2.16 (m, 2 H) 2.96 (m, 1H) 3.92 (s, 3 H) 5.25 (s, 2 H) 6.39 (t, J=6.87 Hz, 1 H) 7.31-7.41 (m, 6 H) 7.60 (dd, J=7.17, 1.98 Hz, 1 H) 7.71 (d, J=8.55 Hz, 1 H) 7.84 (d, J=8.55 Hz, 1 H) 8.07 (s, 1 H) 10.32 (s, 1 H).

Workup

  1. customThe mixture was degassed
  2. customby evacuating the reaction flask
  3. customflushing with N2
  4. filtrationThe reaction mixture was then filtered
  5. concentrationconcentrated in vacuo
  6. customthe resultant residue was purified by silica gel flash chromotagraphy

Sources & evidence

ORD record
ord-a3af55ff931c4f3bb9b8ae4b3f501997
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

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