Sodium Carbonate → HCID 58107384, compound

HRID 1970933Notes

Reaction equation

HRID 1970933 reaction equation
Br[C:2]1[N:3]([CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[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.C([C:36]1[C:41]([NH2:42])=[CH:40][CH:39]=[CH:38][C:37]=1B1OC(C)(C)C(C)(C)O1)(OC(C)(C)C)=O.[C:52]([O-:55])([O-])=[O:53].[Na+].[Na+].[Li+].[Cl-]>C1(C)C=CC=CC=1.CCO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:25]([O:24][C:22](=[O:23])[CH2:21][N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2)[C:10]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:2]1[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][C:41]=1[NH:42][C:52]([O:55][C:6]([CH3:17])([CH3:7])[CH3:5])=[O:53])([CH3:28])([CH3:27])[CH3:26]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 299433152-Bromo-1-tert-butoxycarbonylmethyl-3-cyclohexyl-1H-indole-6-carboxylic acid methyl esterHCID 131730531HCID 131730531, compound

Product 1

HCID 58107384HCID 58107384, compoundYield 181.8%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 2-bromo-1-(2-tert-butoxy-2-oxoethyl)-3-cyclohexyl-1H-indole-6-carboxylate (5.0 g, 11 mmol), (2-BOC-aminophenyl)boronic acid pinacol ester (5.3 g, 16 mmol), and tetrakis (triphenylphosphine)-palladium (0) (1.3 g, 1.1 mmol) in toluene/EtOH (1:1, 80 mL) was added Na2CO3 (3.0 g, 28 mmol), aq. LiCl (2.0M, 22 mL, 44 mmol) and H2O (5 mL). The mixture was refluxed at 100° C. for 2 h, and then the organic solvents were removed under vacuum. The residue is partitioned between EtOAc and water and the organic layer was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by silica gel chromatography (SiO2, EtOAc in hexanes, 5%˜40%) to yield methyl 1-(2-tert-butoxy-2-oxoethyl)-2-(2-(tert-butoxycarbonylamino)phenyl)-3-cyclohexyl-1H-indole-6-carboxylate (5.7 g, 10 mmol, 92%) as white solid. LCMS: m/e 563 (M+H)+, ret time 2.52 min.

Workup

  1. customthe organic solvents were removed under vacuum
  2. customThe residue is partitioned between EtOAc and water
  3. dry with materialthe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by silica gel chromatography (SiO2, EtOAc in hexanes, 5%˜40%)

Sources & evidence

ORD record
ord-a4e4629f551349eab03fb33667d770d6
Source dataset
uspto-grants-2013_04
Patent number
US08431568B2

Reaction notes

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