Sodium Carbonate → HCID 69204244, compound

HRID 860717Notes

Reaction equation

HRID 860717 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.[Li+].[Cl-].[C:23]([O-:26])([O-])=[O:24].[Na+].[Na+].CC1(C)C(C)(C)OB([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2NC(=O)OC(C)(C)C)O1>C1(C)C=CC=CC=1.CCO.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:6]([O:26][C:23]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[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)=[O:24])([CH3:17])([CH3:7])[CH3:5]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 2773231tert-Butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 69204244HCID 69204244, compoundYield 153.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A slurry of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (1.75 g, 5.22 mmol), LiCl (880 mg, 21.0 mmol), 1M aqueous Na2CO3 (13 mL, 13.0 mmol), Pd(PPh3)4 (600 mg, 0.52 mmol) and tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (2.5 g, 7.8 mmol) in toluene (19 mL) and EtOH (19 mL) was heated at relfux for 2 h. The reaction mixture was cooled and concentrated to dryness under vacuum. The residue was treated with H2O (120 mL) and extracted with EtOAc(2×200 mL). The combined organics were washed with brine (2×20 mL), dried (MgSO4), filtered, concentrated and purified by SiO2 chromatography (5–25% EtOAc/hexanes) to yield methyl 2-(2-(tert-butoxycarbonyl)phenyl)-3-cyclohexyl-1H-indole-6-carboxylate (1.8 g, 4.0 mmol, 77%) as a yellow-pink solid. 1HNMR (500 MHz, CDCl3) δ. 8.26 (d, J=8.5 Hz, 1H), 8.14 (s, 1H), 8.11 (s, 1 H), 7.86 (d, J=8.2 Hz, 1H), 7.82 (dd, J=8.2, 1.5 Hz, 1H), 7.43 (ddd, J=8.5, 7.3, 1.5 Hz, 1H), 7.28 (d, J=7.6, 1.5 Hz, 1H), 7.11 (ddd, J=7.6, 7.3, 1.2 Hz, 1H), 6.67 (br s, 1H), 3.94 (s, 3H), 2.56 (tt, J=12.1, 3.5 Hz, 1H), 1.97–1.22 (m, 10H), 1.45 (s, 9H). LCMS: m/e 449 (M+H)+, ret time 2.39 min, column C, 2 minute gradient, start at 0% B.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated to dryness under vacuum
  3. additionThe residue was treated with H2O (120 mL)
  4. extractionextracted with EtOAc(2×200 mL)
  5. washThe combined organics were washed with brine (2×20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by SiO2 chromatography (5–25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-390be75ea8d14cb6ab10a42e4d61bcc3
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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