Diphenyl Ether → benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(6-methoxy-1H-indol-2-yl)nicotinate

HRID 1481790Notes

Reaction equation

HRID 1481790 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.[F-].[K+].[CH2:24]([O:31][C:32]1[N:47]=[C:46](Cl)[C:45]([CH2:49][CH3:50])=[C:44]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C:33]=1[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C1(OC2C=CC=CC=2)C=CC=CC=1>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:24]([O:31][C:32]1[N:47]=[C:46]([C:9]2[NH:8][C:16]3[C:11]([CH:10]=2)=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=3)[C:45]([CH2:49][CH3:50])=[C:44]([O:51][CH2:52][C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:33]=1[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 7583Diphenyl EtherHCID 522689Potassium FluorideHCID 223094576-Methoxy-1H-indole-2-boronic acid, N-BOC protectedHCID 86280413Benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinate

Product 1

HCID 71284904benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(6-methoxy-1H-indol-2-yl)nicotinateYield 64%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (1-(tert-butoxycarbonyl)-6-methoxy-1H-indol-2-yl)boronic acid (437 mg, 1.5 mmol), Pd2dba3 (23 mg, 0.025 mmol), KF (174 mg, 3.0 mmol), t-Bu3PHBF4 (17.4 mg, 0.06 mmol) and benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinate (488 mg, 1.0 mmol) in THF (2.0 mL) was stirred at 60° C. under argon overnight. The solvent was then replaced with diphenyl ether (2.0 mL) and the mixture was stirred at 180° C. for 1 h. After cooling, the reaction mixture was loaded on a silica gel column and the product was eluted with ethyl acetate in hexanes (0-30% gradient) to furnish benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(6-methoxy-1H-indol-2-yl)nicotinate (380 mg) in 64% yield.

Workup

  1. stirringthe mixture was stirred at 180° C. for 1 h
  2. temperatureAfter cooling
  3. washthe product was eluted with ethyl acetate in hexanes (0-30% gradient)

Sources & evidence

ORD record
ord-43d62eed5aaf4122b46fc178386fb2f5
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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