2-Formylphenylboronic acid → methyl 11-cyclohexyl-6-hydroxy-6H-isoindolo[2,1-a]indole-3-carboxylate

HRID 272546Notes

Reaction equation

HRID 272546 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[CH:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O)=[O:22].[Li+].[Cl-].CCO.C1(C)C=CC=CC=1>C([O-])([O-])=O.[Na+].[Na+].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>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([O:19][CH3:20])=[O:18])=[CH:7][CH:8]=3)[N:3]3[CH:21]([OH:22])[C:23]4[C:28]([C:2]=23)=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 2921892-Formylphenylboronic acidHCID 433294Lithium ChlorideHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylateHCID 21863594Toluene ethanol

Product 1

HCID 11552259methyl 11-cyclohexyl-6-hydroxy-6H-isoindolo[2,1-a]indole-3-carboxylateYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

A stirred mixture of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (10.1 g, 30 mmol), 2-formylphenylboronic acid (5.4 g, 36 mmol), LiCl (3.8 g (90 mmol) and Pd (PPh3)4 (1.6 g, 1.38 mmol) in 1M Na2CO3 (40 mL) and 1:1 EtOH-toluene (180 mL) was heated under nitrogen at 85° C. for 3 hours. The reaction mixture was then cooled to RT, and extracted with EtOAc (2×100 mL). The extracts were washed sequentially with water and brine, then dried (MgSO4), filtered and conventrated in-vacuo to afforded 13.3 g of crude product. This material was triturated with DCM and hexanes to provide pure desired product (7.52 g, 70%). LC-MS: m/e 360 (M−H); 344 (M−17)+. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.33-1.60 (m, 4H) 1.77-2.01 (m, 6H) 2.80 (d, J=11.83 Hz, 1H) 3.02-3.18 (m, 1H) 3.89 (s, 3H) 6.49 (d, J=11.33 Hz, 1H) 7.34 (t, J=7.55 Hz, 1H) 7.46 (t, J=7.55 Hz, 1H) 7.62 (d, J=7.30 Hz, 1H) 7.66-7.74 (m, 2H) 7.77 (d, J=7.81 Hz, 1H) 8.21 (s, 1H).

Workup

  1. temperatureThe reaction mixture was then cooled to RT
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe extracts were washed sequentially with water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customto afforded 13.3 g of crude product
  7. customThis material was triturated with DCM and hexanes

Sources & evidence

ORD record
ord-8698080b1084444496affbe065084404
Source dataset
uspto-grants-2008_11
Patent number
US07456167B2

Reaction notes

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