Sodium Carbonate → methyl 4'-[2-[N-(tert-butoxycarbonyl)-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-1,1'-biphenyl-4-carboxylate

HRID 1823123Notes

Reaction equation

HRID 1823123 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH2:18][C@@H:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=2)[OH:20])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1.[CH3:28][O:29][C:30]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)=[O:31].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.O.[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>[C:13]([O:12][C:11]([N:10]([CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:35]2[CH:36]=[CH:37][C:32]([C:30]([O:29][CH3:28])=[O:31])=[CH:33][CH:34]=2)=[CH:3][CH:4]=1)[CH2:18][C@@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=1)[OH:20])=[O:17])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 24823936HCID 24823936, compound

Product 1

HCID 24823620methyl 4'-[2-[N-(tert-butoxycarbonyl)-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-1,1'-biphenyl-4-carboxylateYield 82%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl N-[2-(4-bromophenyl)ethyl]-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]carbamate (435 mg) in 1,2-dimethoxyethane (6 ml) were added 4-methoxycarbonyl-phenyl boronic acid (224 mg), tetrakis(triphenylphosphine)-palladium (55 mg) and aqueous solution of sodium carbonate (2M, 1.0 ml), and the mixture was stirred at 80° C. for 2 hours under nitrogen. The mixture was diluted with ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=3/1) to give methyl 4′-[2-[N-(tert-butoxycarbonyl)-N-[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]-1,1′-biphenyl-4-carboxylate (400 mg).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel (hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-d59ef1b97076438ca05016c83d14de16
Source dataset
uspto-grants-2006_05
Patent number
US07037938B2

Reaction notes

Loading…